Is ERAP2 p.Ser781Thr (c.2342G>C) pathogenic?

ERAP2 p.Ser781Thr (c.2342G>C) is classified Uncertain significance in ERAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0913); Very rare (popmax 0.00669%, eas).

How common is ERAP2 p.Ser781Thr (c.2342G>C) in the general population?

ERAP2 p.Ser781Thr (c.2342G>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ERAP2 p.Ser781Thr (c.2342G>C)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

ERAP2 p.Ser781Thr

c.2342G>C · rs1430819262 · VCV2597247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.28	GERP -0.56
Regional constraint	o/e 1.11	unconstrained · MANE · 7,969 bp · p 0.076 · regional, not allelic
Overall
CADD	19.46	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,874 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000342% 5/1,461,688 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,958
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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.Ser781Thr
Coding: c.2342G>C
MANE Select: NM_001040458 · reported on NM_022350
dbSNP: rs1430819262
Type: single nucleotide variant
Location: chr5:96909752 (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-ser781thr (accessed [today's date]).

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