Is ERAP1 p.Asp575Asn (c.1723G>A) pathogenic?

ERAP1 p.Asp575Asn (c.1723G>A) is classified Benign in ERAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.0663); Common (popmax 22.3%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ERAP1 p.Asp575Asn (c.1723G>A)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

ERAP1 p.Asp575Asn

Q: How common is ERAP1 p.Asp575Asn (c.1723G>A) in the general population?

ERAP1 p.Asp575Asn (c.1723G>A) is common (popmax 22.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1723G>A · rs10050860 · VCV2688495

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 22.3%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.10	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 0.61	GERP 0.99, phastCons 0.92
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.11 · regional, not allelic
Overall
CADD	16.59	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 22.3% European (non-Finnish) · 261,656/1,175,734 alleles

Filtering AF 22.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.2%

Overall 19.5% 313,739/1,608,984 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	22.3%	4
Finnishnot grpmax-eligible	19.4%	5
Remaining individualsnot grpmax-eligible	17.8%	6
Ashkenazi Jewishnot grpmax-eligible	12.7%	8
Amishnot grpmax-eligible	11.8%	8
Admixed American	10.5%	9
South Asian	9.69%	10
Middle Eastern	9.68%	10
African / African-American	9.28%	11
East Asian	4.54%	22

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.Asp575Asn
Coding: c.1723G>A
MANE Select: NM_001040458
dbSNP: rs10050860
Type: single nucleotide variant
Location: chr5:96786506 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.78 · 27 PDB
Residue 575: a UniProt-annotated variant site (in); a β-strand

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-asp575asn (accessed [today's date]).

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