Is EDA p.Ala361Thr (c.1081G>A) pathogenic?

EDA p.Ala361Thr (c.1081G>A) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). AlphaMissense: ambiguous (0.3775); Very rare (popmax 0.00536%, afr).

How common is EDA p.Ala361Thr (c.1081G>A) in the general population?

EDA p.Ala361Thr (c.1081G>A) is very rare (popmax 0.00536%, afr) (gnomAD).

What do computational predictors say about EDA p.Ala361Thr (c.1081G>A)?

AlphaMissense predicts ambiguous (score 0.3775) — an in-silico prediction, not a clinical call.

EDA p.Ala361Thr

c.1081G>A · VCV3341955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Computational evidence

Protein change
AlphaMissense	0.3775	ambiguous
REVEL	0.606	indeterminate
SaProt	LLR -7.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	23.8	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 0.00536% African / African-American · 3/55,989 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000694%

Overall 0.000663% 8/1,206,233 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,663
South Asian	0.00354%	28,248
European (non-Finnish)	0.000335%	298,134

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: EDA
Protein: p.Ala361Thr
Coding: c.1081G>A
MANE Select: NM_001399
Type: single nucleotide variant
Location: chrX:70035514 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 361: a β-strand; the thd domain

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

Similar variants

EDA p.Ala361= Benign ★ same residue
EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same type
EDA c.526+5G>T Likely pathogenic ★★ same type
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same type
EDA c.707-13T>G Pathogenic ★★ same type
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.924+1G>T Likely pathogenic ★★ 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/eda-p-ala361thr (accessed [today's date]).

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