Is EDAR p.Leu353Phe (c.1057C>T) pathogenic?

EDAR p.Leu353Phe (c.1057C>T) is classified Uncertain significance in EDAR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-17). AlphaMissense: likely pathogenic (0.9314); Absent from gnomAD v4.1; Associated with ectodermal dysplasia 10B, hypohidrotic/hair/tooth type, autosomal recessive.

What condition is associated with EDAR p.Leu353Phe (c.1057C>T)?

EDAR p.Leu353Phe (c.1057C>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.Leu353Phe (c.1057C>T) in the general population?

EDAR p.Leu353Phe (c.1057C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDAR p.Leu353Phe (c.1057C>T)?

AlphaMissense predicts likely pathogenic (score 0.9314) — an in-silico prediction, not a clinical call.

EDAR p.Leu353Phe

c.1057C>T · rs2470613911 · VCV2442005

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9314 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9314	likely pathogenic
REVEL	0.546	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDAR
Protein: p.Leu353Phe
Coding: c.1057C>T
MANE Select: NM_006267 · reported on NM_022336
dbSNP: rs2470613911
Type: single nucleotide variant
Location: chr2:108897197 (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

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

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-leu353phe (accessed [today's date]).

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