Is EDARADD p.Pro52Ser (c.154C>T) pathogenic?

EDARADD p.Pro52Ser (c.154C>T) is classified Uncertain significance in EDARADD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-06). AlphaMissense: likely benign (0.2996); Very rare (popmax 0.0011%, sas); Associated with ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant.

What condition is associated with EDARADD p.Pro52Ser (c.154C>T)?

EDARADD p.Pro52Ser (c.154C>T) is associated with ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant, ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (ClinVar).

How common is EDARADD p.Pro52Ser (c.154C>T) in the general population?

EDARADD p.Pro52Ser (c.154C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EDARADD p.Pro52Ser (c.154C>T)?

AlphaMissense predicts likely benign (score 0.2996) — an in-silico prediction, not a clinical call.

EDARADD p.Pro52Ser

c.154C>T · rs1259703946 · VCV2939545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.2996	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 88 kb · p 0.0061 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,002 alleles

Overall 6.21e-05% 1/1,609,646 alleles · very rare exomes 1/1,457,528 · genomes 0/152,118 · joint denominator

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: EDARADD
Protein: p.Pro52Ser
Coding: c.154C>T
MANE Select: NM_145861
dbSNP: rs1259703946
Type: single nucleotide variant
Location: chr1:236414293 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.81

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

Disease context

ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive

Similar variants

EDARADD p.Arg66Ter Pathogenic ★★ same condition
EDARADD p.Arg170Gln Uncertain significance ★★ ⚠ same condition
EDARADD p.Asp120His Uncertain significance ★★ ⚠ same condition
EDARADD p.Gln8Glu Uncertain significance ★★ ⚠ same condition
EDARADD p.Gly74Arg Uncertain significance ★★ ⚠ same condition
EDARADD c.120+7G>A Benign ★★ same condition
EDARADD c.121-19C>T Benign ★★ same condition
EDARADD c.161-13T>C Benign/Likely benign ★★ 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/edaradd-p-pro52ser (accessed [today's date]).

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