Is ERAP2 p.Arg20Thr (c.59G>C) pathogenic?

ERAP2 p.Arg20Thr (c.59G>C) is classified Likely benign in ERAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0919); Very rare (popmax 0.00534%, nfe).

How common is ERAP2 p.Arg20Thr (c.59G>C) in the general population?

ERAP2 p.Arg20Thr (c.59G>C) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about ERAP2 p.Arg20Thr (c.59G>C)?

AlphaMissense predicts likely benign (score 0.0919) — an in-silico prediction, not a clinical call.

ERAP2 p.Arg20Thr

c.59G>C · VCV3845706

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0919	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.24	GERP -3.8
Regional constraint	o/e 0.99	unconstrained · MANE · 30 kb · p 0.75 · regional, not allelic
Overall
CADD	0.079	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 0.00534% European (non-Finnish) · 63/1,180,030 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00397% 64/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,731
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Arg20Thr
Coding: c.59G>C
MANE Select: NM_001040458 · reported on NM_022350
Type: single nucleotide variant
Location: chr5:96879744 (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-arg20thr (accessed [today's date]).

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