Is ERAP2 p.Asp789Val (c.2366A>T) pathogenic?

ERAP2 p.Asp789Val (c.2366A>T) is classified Uncertain significance in ERAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.5266); Very rare (popmax 0.000594%, nfe).

How common is ERAP2 p.Asp789Val (c.2366A>T) in the general population?

ERAP2 p.Asp789Val (c.2366A>T) is very rare (popmax 0.000594%, nfe) (gnomAD).

What do computational predictors say about ERAP2 p.Asp789Val (c.2366A>T)?

AlphaMissense predicts ambiguous (score 0.5266) — an in-silico prediction, not a clinical call.

ERAP2 p.Asp789Val

c.2366A>T · VCV4019130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5266	ambiguous
REVEL	0.385	indeterminate
SaProt	LLR -13.77	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.6	GERP 0.64, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 7,969 bp · p 0.076 · regional, not allelic
Overall
CADD	24.1	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 0.000594% European (non-Finnish) · 7/1,178,524 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000435% 7/1,608,376 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.Asp789Val
Coding: c.2366A>T
MANE Select: NM_001040458 · reported on NM_022350
Type: single nucleotide variant
Location: chr5:96912648 (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-asp789val (accessed [today's date]).

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