Is EDAR p.Val340Met (c.1018G>A) pathogenic?

EDAR p.Val340Met (c.1018G>A) is classified Uncertain significance in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.3942); Very rare (popmax 0.00891%, eas); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

How common is EDAR p.Val340Met (c.1018G>A) in the general population?

EDAR p.Val340Met (c.1018G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about EDAR p.Val340Met (c.1018G>A)?

AlphaMissense predicts ambiguous (score 0.3942) — an in-silico prediction, not a clinical call.

EDAR p.Val340Met

Q: What condition is associated with EDAR p.Val340Met (c.1018G>A)?

EDAR p.Val340Met (c.1018G>A) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.1018G>A · rs779487722 · VCV2948164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.3942	ambiguous
REVEL	0.324	indeterminate
SaProt	LLR -7.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.00891% East Asian · 4/44,892 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00112% 18/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
African / African-American	0.004%	24,975
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,092
European (non-Finnish)	0.000508%	196,672

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: EDAR
Protein: p.Val340Met
Coding: c.1018G>A
MANE Select: NM_022336
dbSNP: rs779487722
Type: single nucleotide variant
Location: chr2:108906314 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB

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

Disease context

ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive hypohidrotic ectodermal dysplasia

Similar variants

EDAR p.Val340Leu Likely pathogenic ★ ⚠ same residue
EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg25Ter Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg358Ter Pathogenic ★★ same condition
EDAR p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Arg89His Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Cys301Ter 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/edar-p-val340met (accessed [today's date]).

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