Is ERAP2 p.Arg293Trp (c.877C>T) pathogenic?

ERAP2 p.Arg293Trp (c.877C>T) is classified Likely benign in ERAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely benign (0.0471); Rare (popmax 0.264%, mid).

How common is ERAP2 p.Arg293Trp (c.877C>T) in the general population?

ERAP2 p.Arg293Trp (c.877C>T) is rare (popmax 0.264%, mid) (gnomAD).

What do computational predictors say about ERAP2 p.Arg293Trp (c.877C>T)?

AlphaMissense predicts likely benign (score 0.0471) — an in-silico prediction, not a clinical call.

ERAP2 p.Arg293Trp

c.877C>T · rs776167404 · VCV2375745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0471 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.264%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0471	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.24	loss · gain 0.03 · independent
Constraint at this position
Conservation	phyloP -1.5	GERP -4.8
Regional constraint	o/e 0.99	unconstrained · MANE · 30 kb · p 0.75 · regional, not allelic
Overall
CADD	4.585	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% Middle Eastern · 16/6,060 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.00446% 72/1,614,114 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.264%	379
African / African-American	0.00933%	10,722
South Asian	0.00659%	15,180
European (non-Finnish)	0.00347%	28,780
Remaining individualsnot grpmax-eligible	0.0032%	31,254

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERAP2
Protein: p.Arg293Trp
Coding: c.877C>T
MANE Select: NM_001040458 · reported on NM_022350
dbSNP: rs776167404
Type: single nucleotide variant
Location: chr5:96889212 (GRCh38)

Full ERAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/erap2-p-arg293trp (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown