Is EDAR p.Arg25Ter (c.73C>T) pathogenic?

EDAR p.Arg25Ter (c.73C>T) is classified Pathogenic/Likely pathogenic in EDAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-22). Very rare (popmax 0.00333%, amr); Associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant.

How common is EDAR p.Arg25Ter (c.73C>T) in the general population?

EDAR p.Arg25Ter (c.73C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

EDAR p.Arg25Ter

Q: What condition is associated with EDAR p.Arg25Ter (c.73C>T)?

EDAR p.Arg25Ter (c.73C>T) is associated with ectodermal dysplasia 10A, hypohidrotic/hair/nail type, autosomal dominant, autosomal recessive hypohidrotic ectodermal dysplasia (ClinVar).

c.73C>T · rs773132518 · VCV2203127

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 12
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.8	GERP -5
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000558% 9/1,613,948 alleles · very rare exomes 7/1,461,802 · genomes 2/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,242
East Asian	0.00223%	44,880
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,345

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.Arg25Ter
Coding: c.73C>T
MANE Select: NM_022336
dbSNP: rs773132518
Type: single nucleotide variant
Location: chr2:108930221 (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.Ala26Val 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
EDAR p.Cys428Arg Pathogenic/Likely pathogenic ★★ same condition
EDAR p.Gly382Ser 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-arg25ter (accessed [today's date]).

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