Is ETAA1 p.Ala83Pro (c.247G>C) pathogenic?

ETAA1 p.Ala83Pro (c.247G>C) is classified Uncertain significance in ETAA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely benign (0.1125); Ultra-rare (popmax 0.0106%, nfe).

How common is ETAA1 p.Ala83Pro (c.247G>C) in the general population?

ETAA1 p.Ala83Pro (c.247G>C) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about ETAA1 p.Ala83Pro (c.247G>C)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

ETAA1 p.Ala83Pro

c.247G>C · rs199959789 · VCV2283331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.04	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 -0.44	GERP -4.3, phastCons 0.002
Regional constraint	o/e 1.04	unconstrained · MANE · 7,112 bp · p 0.28 · regional, not allelic
Overall
CADD	9.332	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 0.0106% European (non-Finnish) · 125/1,179,412 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00845%

Overall 0.008% 129/1,612,798 alleles · ultra-rare exomes 115/1,460,602 · genomes 14/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,435
South Asian	0.0022%	45,408
Remaining individualsnot grpmax-eligible	0.0016%	62,428
Finnishnot grpmax-eligible	0.00156%	64,010

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: ETAA1
Protein: p.Ala83Pro
Coding: c.247G>C
MANE Select: NM_019002
dbSNP: rs199959789
Type: single nucleotide variant
Location: chr2:67399192 (GRCh38)
Gene constraint: LOEUF 0.849 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.74 · 5 PDB
Residue 83: the 'disordered' region

Full ETAA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ETAA1 p.Glu588= Benign ★★ same type
ETAA1 p.Pro861= Benign ★★ same type
ETAA1 p.Ala40Val Uncertain significance ★ ⚠ same type
ETAA1 p.Ala48Pro Uncertain significance ★ ⚠ same type
ETAA1 p.Ala48Val Uncertain significance ★ ⚠ same type
ETAA1 p.Ala544Val Uncertain significance ★ ⚠ same type
ETAA1 p.Ala586Thr Uncertain significance ★ ⚠ same type
ETAA1 p.Ala920Ser 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/etaa1-p-ala83pro (accessed [today's date]).

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