Is EDA p.Gln247Arg (c.740A>G) pathogenic?

EDA p.Gln247Arg (c.740A>G) is classified Uncertain significance in EDA (ClinVar, Single submitter, 2 submitters; last evaluated 2011-09-20). AlphaMissense: likely benign (0.3037); Absent from gnomAD v4.1.

How common is EDA p.Gln247Arg (c.740A>G) in the general population?

EDA p.Gln247Arg (c.740A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Gln247Arg (c.740A>G)?

AlphaMissense predicts likely benign (score 0.3037) — an in-silico prediction, not a clinical call.

EDA p.Gln247Arg

c.740A>G · rs397516673 · VCV44206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3037 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3037	likely benign
REVEL	0.548	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.83	donor loss · deltas
Pangolin	Δ0.61	loss · gain 0.21 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 4.5, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Gln247Arg
Coding: c.740A>G
MANE Select: NM_001399
dbSNP: rs397516673
Type: single nucleotide variant
Location: chrX:70029537 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB

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

Similar variants

EDA p.Gln247His Uncertain significance ★★ ⚠ same residue
EDA p.Gln247= Pathogenic ★ same residue
EDA p.Gln247Ter 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

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-gln247arg (accessed [today's date]).

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