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151 Pestilence
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156 Captain
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170 Clemens
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173 Mei
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177 Hankerson
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188 Brian
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193 Mary Xavier
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148. I'll allow; he should be designated Earth-16 but that version is the only one to use all three names; on Earth-1/Earth-Prime, John Jr. and Connor are separate characters. Beyond that, everyone is correct; list updated. Mxyzptlk appears here in his original look.
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Remaining clues:
199. Original; medical doctor; treated a cast character who is a sibling to another cast character KA*LA*
208. Real person (at least going by first name); unrevealed; sought autograph from heroes; does he look familiar somehow? Actor who played him is better known for non-acting work. *ARV [LOCKED; characters found at time of locking: ABDEFGHJKLORTVWYZ13457890]
210. Original, though shares name with comics character; unrevealed; once erroneously believed to have killed a major character; interrogated by cast character *KEL [LOCKED; characters found at time of locking: EFGHJKLORTU3457]
211. Original; bank robber; sent to steal for comics based/time motif villain *ERTO [LOCKED; characters found at time of locking: EFGHJKORT345]
212. Original; criminal; prisoner in other dimensional realm; name refers to an injury of some sort S*AR [LOCKED; characters found at time of locking: ABDEFGHJKLORSTVWYZ13457890]
219. Original; criminal; joined major villain's army; nname refers to a kind if physique R***ED
222. Original; pirate; lover of famous 18th century pirate A**E QUEE* [LOCKED; all remaing letters the same; characters found at time of locking: ABDEFGHJKLOQRSTVWYZ13457890]
223. Original; film director; did documentary on main character; followed hero in pursuit of #76 MAR**A *EDOW*TZ
228. Original; crime family consigliere; killed by boss' daughter out of a revenge for a kill he did ***K SALVAT*
232. Original; government agent; from China but killed in New Zealand; used Darryl as an alias SE* M**G
236. Original; high school football coach; allowed main character to be assistant coach GA**ES
237. Comics; police commissioner; disapproved of main character's actions; while not killed off, only seen in one episode; Green Arrow BR*A* *UDO*ERDO
239. Original; unrevealed; husband of long recurring police character RO* [LOCKED; characters found at time of locking: EFGHJKORT345]
253. Original; board member; got major character ousted from tech company they were running DE***S
256. Original; shopkeeper; active in the near future; shares name with famous non-DC feline character FEL**
257. Comics (somewhat different name); assassin; second in command in her organization which operates out of an island; Batwoman: Rebirth TAT*A*A
268. Original; probably none so far, possibly student; foster daughter of major characters, one of who was a cast character the entire series ES*E [LOCKED; characters found at time of locking: ABDEFGHJKLORSTVWYZ13457890]
271. Original; member of resistance group; extra-terrestrial; IIRC has never been to Earth *'KEYY [LOCKED; characters found at time of locking: BDEFGHJKLORTWYZ1345790]
277. Original; Washington DC senator with an interest in extra-terrestrials GRA*BERRY [LOCKED; characters found at time of locking: ABDEFGHJKLORTVWYZ13457890]
279. Original; attorney; did pro-bono work for company major character worked at during sabbatical from her main employer A*ASTAS*A
301. Somewhat based on comics (gender swapped), though another character has the comics version's abilities; quantum engineer/CEO; was replaced by a doppelgänger who posed as her; her doppelgänger first appeared before she did; Animal Man EVA M**ULLO*H [LOCKED; all remaining letters the same; characters found at time of locking: ABDEFGHJKLMOQRSTVWYZ13457890]
302. Original; police officer; betrayed his PD to a super-villain; was not a villain in the season he first appeared in JO*ES [LOCKED; characters found at time of locking: ABDEFGHJKLORSTVWYZ13457890]
303. Original; student; wore homemade costume based on main character that she later threw in the trash L*UR*[LOCKED; both remaining letters the same; characters found at time of locking: EFGHJKLORT3457]
305. Original; high school student seeking Hudson University admission HE*RY *EUMA* [LOCKED; both remaining letters the same; characters found at time of locking: ABDEFGHJKLMOQRSTVWYZ13457890]
307. Comics; criminal; wrongly imprisoned for false confession; became thief upon release; Supergirl MURMUR / M**HAEL AMAR
308. Original; mixed martial arts fighter; affected by humanity totem being activated *GOR STARROS [LOCKED; characters found at time of locking: ABDEFGHJKLORSTVWYZ13457890]
309. Original; waitress; dropped food and drinks after bumping into co-worker; only appearance was in a series pilot TRA*Y [LOCKED; characters found at time of locking: ABDEFGHJKLORTVWYZ13457890]
310. Original; singer; from Old West; briefly inside a time machine *OWBOY *ARRATOR
311. Original; computer hacker; spent five years in prison; seduced by someone who killed him K*RBY BATES [LOCKED; characters found at time of locking: ABDEFGHJKLORSTVWYZ13457890]
312. Original; fence; tried to steal from jewel thief; alive from 1968 to 2013 *ASS DERE***K
313. Comics (but this name not used in comics); CEO; masterminded an outbreak of tuberculosis; son was a the main villain of a season; Vigilante JUST** *LAYBOUR*E
314. Comics; unrevealed if applicable; demonic rival to cast character; only seen in Hell; Hellblazer *AL*BRA**S
315. Original; criminal; worked for comics-based villain wi8th time motif EDD*E WAL*Z*K
316. Original; Museum of Antiquities curator; super-villain stole necklace she had obtained permission to exhibit *O*A**A
317. Original; maid; murdered by employer; only seen in flashbacks GAL**A VE*ED*KTOV
318. Original; shop owner; aunt of super-villain; Irish S**EAD
319. Original; drug dealer; sold drugs to cast character at a mansion JORDA* KER* [LOCKED; both remaining letters the same; characters found at time of locking: ABDEFGHJKLORTVWYZ13457890]
320. Original; artifacts collector; attacked by super-villain he was showing his collection to *HR*STO*H BA*KS
321. Original; unrevealed; possible professional fighter; part of super-villain's fight club; a Brevakk QU*LL [LOCKED; characters found at time of locking: ABDEFGHJKLOQRSTVWYZ13457890]
342. Original; probable student when last seen; boyfriend of #325 in Harmony Falls TO**Y FULLER [LOCKED; characters found at time of locking: BDEFGHJKLORTWYZ1345790]
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199. Kaplan
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219. Ripped
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223. Marcia Pedowitz
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228. Nick Salvati
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232. Sen Ming
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236. Gaines
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237. Brian Nudocerdo
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253. Dennis
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257. Tatiana
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279. Anastasia
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307. Murmer/Michael Amar
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310. Cowboy Narrator
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312. Cass Derenick
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313. Justin Claybourne
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314. Calibraxis
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315. Eddie Walczak
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317. Galina Venediktov
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318. Sinead
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320. Christoph Banks
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222. Anne Queen
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301. Eva McCulloch