Is ERAP1 p.Val58Ile (c.172G>A) pathogenic?

ERAP1 p.Val58Ile (c.172G>A) is classified Likely benign in ERAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0683); Very rare (popmax 0.00538%, afr).

How common is ERAP1 p.Val58Ile (c.172G>A) in the general population?

ERAP1 p.Val58Ile (c.172G>A) is very rare (popmax 0.00538%, afr) (gnomAD).

What do computational predictors say about ERAP1 p.Val58Ile (c.172G>A)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

ERAP1 p.Val58Ile

c.172G>A · VCV4019117

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00538%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.074	GERP -3.6, phastCons 0.001
Regional constraint	o/e 0.86	unconstrained · MANE · 10 kb · p 0.003 · regional, not allelic
Overall
CADD	12.55	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 0.00538% African / African-American · 4/74,394 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00124% 20/1,613,490 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00538%	18,598
East Asian	0.00445%	22,448
Admixed American	0.00333%	29,992
South Asian	0.0022%	45,545
Remaining individualsnot grpmax-eligible	0.0016%	62,468
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.000678%	147,505

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.Val58Ile
Coding: c.172G>A
MANE Select: NM_001040458
Type: single nucleotide variant
Location: chr5:96803755 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.78 · 27 PDB
Residue 58: a β-strand

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

Similar variants

ERAP1 p.Val58Leu Uncertain significance ★ ⚠ same residue
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

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-val58ile (accessed [today's date]).

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