Is EDA p.Arg384Thr (c.1151G>C) pathogenic?

EDA p.Arg384Thr (c.1151G>C) is classified Uncertain significance in EDA (ClinVar, Single submitter, 1 submitter; last evaluated 2012-02-01). AlphaMissense: likely pathogenic (0.9923); Absent from gnomAD v4.1.

How common is EDA p.Arg384Thr (c.1151G>C) in the general population?

EDA p.Arg384Thr (c.1151G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Arg384Thr (c.1151G>C)?

AlphaMissense predicts likely pathogenic (score 0.9923) — an in-silico prediction, not a clinical call.

EDA p.Arg384Thr

c.1151G>C · rs397516655 · VCV44186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9923	likely pathogenic · top 10% in EDA
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -13.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
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	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Arg384Thr
Coding: c.1151G>C
MANE Select: NM_001399
dbSNP: rs397516655
Type: single nucleotide variant
Location: chrX:70035584 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 384: a β-strand; the thd domain

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

Similar variants

EDA p.Arg384Ser Likely pathogenic ★★ same residue
EDA p.Arg384Gly Likely pathogenic ★ 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

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-arg384thr (accessed [today's date]).

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