Is ERAP2 p.Phe905Ser (c.2714T>C) pathogenic?

ERAP2 p.Phe905Ser (c.2714T>C) is classified Uncertain significance in ERAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.6979); Very rare (popmax 0.00135%, afr).

How common is ERAP2 p.Phe905Ser (c.2714T>C) in the general population?

ERAP2 p.Phe905Ser (c.2714T>C) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about ERAP2 p.Phe905Ser (c.2714T>C)?

AlphaMissense predicts likely pathogenic (score 0.6979) — an in-silico prediction, not a clinical call.

ERAP2 p.Phe905Ser

c.2714T>C · VCV4665044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6979	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -15.01	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,969 bp · p 0.076 · regional, not allelic
Overall
CADD	23.0	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 0.00135% African / African-American · 1/74,304 alleles

Overall 6.9e-05% 1/1,448,358 alleles · very rare

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.Phe905Ser
Coding: c.2714T>C
MANE Select: NM_001040458 · reported on NM_022350
Type: single nucleotide variant
Location: chr5:96915744 (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-phe905ser (accessed [today's date]).

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