Is ERAP1 p.Ser897Pro (c.2689T>C) pathogenic?

ERAP1 p.Ser897Pro (c.2689T>C) is classified Uncertain significance in ERAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.3099); Ultra-rare (popmax 0.0164%, mid).

How common is ERAP1 p.Ser897Pro (c.2689T>C) in the general population?

ERAP1 p.Ser897Pro (c.2689T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ERAP1 p.Ser897Pro (c.2689T>C)?

AlphaMissense predicts likely benign (score 0.3099) — an in-silico prediction, not a clinical call.

ERAP1 p.Ser897Pro

c.2689T>C · rs554933786 · VCV2383172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3099	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.88, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.11 · regional, not allelic
Overall
CADD	25.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.00762% 123/1,613,930 alleles · ultra-rare exomes 115/1,461,674 · genomes 8/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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: ERAP1
Protein: p.Ser897Pro
Coding: c.2689T>C
MANE Select: NM_001040458
dbSNP: rs554933786
Type: single nucleotide variant
Location: chr5:96776533 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.78 · 27 PDB
Residue 897: an α-helix

Full ERAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERAP1 p.Ala356= Benign ★★ same type
ERAP1 p.Gly514Arg Benign/Likely benign ★★ same type
ERAP1 p.Ile915Thr Likely benign ★★ ⚠ same type
ERAP1 p.Ser18= Benign/Likely benign ★★ same type
ERAP1 p.Tyr57= Benign/Likely benign ★★ same type
ERAP1 p.Tyr789= Benign ★★ same type
ERAP2 p.Leu411Arg Benign/Likely benign ★★ ⚠ same type
CAST p.Leu618Phe Uncertain significance ★ ⚠ same type

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/erap1-p-ser897pro (accessed [today's date]).

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