Is EDA p.Trp274Arg (c.820T>C) pathogenic?

EDA p.Trp274Arg (c.820T>C) is classified Likely pathogenic in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-13). AlphaMissense: likely pathogenic (1); Absent from gnomAD v4.1; Associated with EDA-related disorder.

What condition is associated with EDA p.Trp274Arg (c.820T>C)?

EDA p.Trp274Arg (c.820T>C) is associated with EDA-related disorder (ClinVar).

How common is EDA p.Trp274Arg (c.820T>C) in the general population?

EDA p.Trp274Arg (c.820T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Trp274Arg (c.820T>C)?

AlphaMissense predicts likely pathogenic (score 1) — an in-silico prediction, not a clinical call.

EDA p.Trp274Arg

c.820T>C · rs2520343091 · VCV2635389

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

1 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EDA-related disorder

Computational evidence

Protein change
AlphaMissense	1	likely pathogenic ✓ concordant with ClinVar · top 2% in EDA
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -14.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 4.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	32.0	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.Trp274Arg
Coding: c.820T>C
MANE Select: NM_001399
dbSNP: rs2520343091
Type: single nucleotide variant
Location: chrX:70033424 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 274: the thd domain; a UniProt-annotated variant site (in xhed)

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

Disease context

EDA-related disorder

Similar variants

EDA p.Trp274Ter Pathogenic ★★ same residue
EDA p.Trp274Cys Likely 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

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-trp274arg (accessed [today's date]).

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