Is EDAR p.Met107Val (c.319A>G) pathogenic?

EDAR p.Met107Val (c.319A>G) is classified Conflicting classifications of pathogenicity in EDAR (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.054); Common (popmax 8.39%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

What condition is associated with EDAR p.Met107Val (c.319A>G)?

EDAR p.Met107Val (c.319A>G) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive, hypohidrotic ectodermal dysplasia (ClinVar).

What do computational predictors say about EDAR p.Met107Val (c.319A>G)?

AlphaMissense predicts likely benign (score 0.054) — an in-silico prediction, not a clinical call.

EDAR p.Met107Val

Q: How common is EDAR p.Met107Val (c.319A>G) in the general population?

EDAR p.Met107Val (c.319A>G) is common (popmax 8.39%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.319A>G · rs61761321 · VCV261572

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.054 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.39%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.054	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	13.98	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 8.39% East Asian · 3,766/44,890 alleles

Filtering AF 8.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.07%

Overall 0.264% 4,264/1,614,160 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	8.39%	12
Remaining individualsnot grpmax-eligible	0.51%	196
South Asian	0.0823%	1,214
African / African-American	0.0733%	1,365
Admixed American	0.0267%	3,752
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00263%	38,066
Finnishnot grpmax-eligible	0.00156%	63,956

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.Met107Val
Coding: c.319A>G
MANE Select: NM_022336
dbSNP: rs61761321
Type: single nucleotide variant
Location: chr2:108929235 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 107: a disulfide bond; a β-strand

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: ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive hypohidrotic ectodermal dysplasia autosomal recessive hypohidrotic ectodermal dysplasia

Similar variants

EDAR p.Met107Ile Uncertain significance ★ ⚠ same residue
EDAR c.730+1G>T Pathogenic ★★ same condition
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

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-met107val (accessed [today's date]).

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