Is EDAR p.Cys31Ter (c.93C>A) pathogenic?

EDAR p.Cys31Ter (c.93C>A) is classified Likely pathogenic in EDAR (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-01). Very rare (popmax 8.47e-05%, nfe); Associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive.

What condition is associated with EDAR p.Cys31Ter (c.93C>A)?

EDAR p.Cys31Ter (c.93C>A) is associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive (ClinVar).

How common is EDAR p.Cys31Ter (c.93C>A) in the general population?

EDAR p.Cys31Ter (c.93C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

EDAR p.Cys31Ter

c.93C>A · rs749688157 · VCV828108

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

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

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.27	loss · gain 0.23 · independent
Constraint at this position
Conservation	phyloP -3.3	GERP -5
Overall
CADD	31.0	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 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,810 alleles · very rare

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.Cys31Ter
Coding: c.93C>A
MANE Select: NM_006267 · reported on NM_022336
dbSNP: rs749688157
Type: single nucleotide variant
Location: chr2:108930201 (GRCh38)

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

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-cys31ter (accessed [today's date]).

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