Is EDAR p.Val284Ile (c.850G>A) pathogenic?

EDAR p.Val284Ile (c.850G>A) is classified Conflicting classifications of pathogenicity in EDAR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0836); Ultra-rare (popmax 0.024%, afr); Associated with Inborn genetic diseases.

How common is EDAR p.Val284Ile (c.850G>A) in the general population?

EDAR p.Val284Ile (c.850G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about EDAR p.Val284Ile (c.850G>A)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

EDAR p.Val284Ile

Q: What condition is associated with EDAR p.Val284Ile (c.850G>A)?

EDAR p.Val284Ile (c.850G>A) is associated with Inborn genetic diseases, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.850G>A · rs138052931 · VCV2194381

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.19	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 2.6	GERP -1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	9.473	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 0.024% African / African-American · 18/74,884 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00366% 59/1,612,418 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,160
Remaining individualsnot grpmax-eligible	0.0224%	4,460
Admixed American	0.00833%	11,998
Finnishnot grpmax-eligible	0.00786%	12,721
East Asian	0.00446%	22,417
South Asian	0.0022%	45,529
European (non-Finnish)	0.0011%	90,694

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.Val284Ile
Coding: c.850G>A
MANE Select: NM_022336
dbSNP: rs138052931
Type: single nucleotide variant
Location: chr2:108907973 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 284: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant autosomal recessive hypohidrotic ectodermal dysplasia

Similar variants

EDAR p.Val284= Likely benign ★ 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-val284ile (accessed [today's date]).

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