Is EDAR p.Arg98Trp (c.292C>T) pathogenic?

EDAR p.Arg98Trp (c.292C>T) is classified Pathogenic/Likely pathogenic in EDAR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.7237); Very rare (popmax 0.00549%, sas); Associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive.

What condition is associated with EDAR p.Arg98Trp (c.292C>T)?

EDAR p.Arg98Trp (c.292C>T) is associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive, ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

How common is EDAR p.Arg98Trp (c.292C>T) in the general population?

EDAR p.Arg98Trp (c.292C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about EDAR p.Arg98Trp (c.292C>T)?

AlphaMissense predicts likely pathogenic (score 0.7237) — an in-silico prediction, not a clinical call.

EDAR p.Arg98Trp

c.292C>T · rs557166582 · VCV532549

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7237 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.7237	likely pathogenic ✓ concordant with ClinVar
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -11.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	29.6	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 0.00549% South Asian · 5/91,092 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00118% 19/1,614,170 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
Finnishnot grpmax-eligible	0.00156%	63,986
European (non-Finnish)	0.0011%	90,772

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.Arg98Trp
Coding: c.292C>T
MANE Select: NM_022336
dbSNP: rs557166582
Type: single nucleotide variant
Location: chr2:108929262 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 98: a disulfide bond; a UniProt-annotated variant site (in ectd10b)

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

Disease context

ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive — 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.Arg98Gln Pathogenic ★ ⚠ 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.Cys148Arg 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-arg98trp (accessed [today's date]).

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