Is OR2A4 p.Glu195Lys (c.583G>A) pathogenic?

OR2A4 p.Glu195Lys (c.583G>A) is classified Uncertain significance in OR2A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0494%, nfe).

How common is OR2A4 p.Glu195Lys (c.583G>A) in the general population?

OR2A4 p.Glu195Lys (c.583G>A) is ultra-rare (popmax 0.0494%, nfe) (gnomAD).

What do computational predictors say about OR2A4 p.Glu195Lys (c.583G>A)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

OR2A4 p.Glu195Lys

c.583G>A · rs768526817 · VCV2566823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.91	GERP -0.93
Regional constraint	o/e 0.20	constrained · MANE · 198 bp · p 6.3e-12 · regional, not allelic
Overall
CADD	13.36	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% European (non-Finnish) · 494/999,182 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.0391% 524/1,338,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0494%	2,023
Remaining individualsnot grpmax-eligible	0.0356%	2,812
African / African-American	0.0184%	5,433
Admixed American	0.0108%	9,248

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: OR2A4
Protein: p.Glu195Lys
Coding: c.583G>A
MANE Select: NM_005021 · reported on NM_030908
dbSNP: rs768526817
Type: single nucleotide variant
Location: chr6:131700819 (GRCh38)

Full OR2A4 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/or2a4-p-glu195lys (accessed [today's date]).

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