Is EDA p.Met373Val (c.1117A>G) pathogenic?

EDA p.Met373Val (c.1117A>G) is classified Conflicting classifications of pathogenicity in EDA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-04). AlphaMissense: likely pathogenic (0.9837); Absent from gnomAD v4.1; Associated with EDA-related disorder.

What condition is associated with EDA p.Met373Val (c.1117A>G)?

EDA p.Met373Val (c.1117A>G) is associated with EDA-related disorder (ClinVar).

How common is EDA p.Met373Val (c.1117A>G) in the general population?

EDA p.Met373Val (c.1117A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Met373Val (c.1117A>G)?

AlphaMissense predicts likely pathogenic (score 0.9837) — an in-silico prediction, not a clinical call.

EDA p.Met373Val

c.1117A>G · VCV3907400

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EDA-related disorder

Computational evidence

Protein change
AlphaMissense	0.9837	likely pathogenic
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.79	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 4.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDA
Protein: p.Met373Val
Coding: c.1117A>G
MANE Select: NM_001399
Type: single nucleotide variant
Location: chrX:70035550 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 373: a UniProt-annotated variant site (in xhed); the thd domain

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

Disease context

EDA-related disorder

Similar variants

EDA p.Met373Ile Pathogenic ★ ⚠ same residue
EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same condition
EDA c.526+5G>T Likely pathogenic ★★ same condition
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same condition
EDA p.Arg153Cys Pathogenic ★★ ⚠ same condition
EDA p.Arg276Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDA p.Arg289Cys Pathogenic ★★ ⚠ same condition
EDA p.Gly299Ser Pathogenic/Likely pathogenic ★★ same condition

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-met373val (accessed [today's date]).

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