Is ECE2 p.Gly82Arg (c.244G>A) pathogenic?

ECE2 p.Gly82Arg (c.244G>A) is classified Uncertain significance in ECE2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.3683); Very rare (popmax 0.00333%, amr).

How common is ECE2 p.Gly82Arg (c.244G>A) in the general population?

ECE2 p.Gly82Arg (c.244G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ECE2 p.Gly82Arg (c.244G>A)?

AlphaMissense predicts ambiguous (score 0.3683) — an in-silico prediction, not a clinical call.

ECE2 p.Gly82Arg

c.244G>A · VCV3506430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Computational evidence

Protein change
AlphaMissense	0.3683	ambiguous
REVEL	0.403	indeterminate
SaProt	LLR -11.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.47, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.014 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G128R vs ClinVar G82R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000867% 14/1,613,892 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,993
European (non-Finnish)	0.00102%	98,333

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: ECE2
Protein: p.Gly82Arg
Coding: c.244G>A
MANE Select: NM_001100121
Type: single nucleotide variant
Location: chr3:184277009 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.75

Full ECE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECE2 p.Arg453Gln Benign ★★ same type
ECE2 p.Ser400= Benign ★★ same type
ECE2 p.Val248= Benign ★★ same type
EEF1AKMT4-ECE2 p.Val127Ala Benign ★★ same type
ECE2 p.Ala338Val Uncertain significance ★ ⚠ same type
ECE2 p.Ala437Thr Uncertain significance ★ ⚠ same type
ECE2 p.Ala575Thr Uncertain significance ★ ⚠ same type
ECE2 p.Ala638Gly 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/ece2-p-gly82arg (accessed [today's date]).

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