Is EDARADD p.Ser103Phe (c.308C>T) pathogenic?

EDARADD p.Ser103Phe (c.308C>T) is classified Benign/Likely benign in EDARADD (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.131); Low-frequency (popmax 3.84%, mid); Associated with hypohidrotic ectodermal dysplasia.

How common is EDARADD p.Ser103Phe (c.308C>T) in the general population?

EDARADD p.Ser103Phe (c.308C>T) is low-frequency (popmax 3.84%, mid) (gnomAD).

How is Hypohidrotic ectodermal dysplasia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about EDARADD p.Ser103Phe (c.308C>T)?

AlphaMissense predicts likely benign (score 0.131) — an in-silico prediction, not a clinical call.

EDARADD p.Ser103Phe

Q: What condition is associated with EDARADD p.Ser103Phe (c.308C>T)?

EDARADD p.Ser103Phe (c.308C>T) is associated with hypohidrotic ectodermal dysplasia, ectodermal dysplasia 11A, hypohidrotic/hair/tooth type, autosomal dominant, ectodermal dysplasia 11B, hypohidrotic/hair/tooth type, autosomal recessive (ClinVar).

c.308C>T · rs114632254 · VCV262601

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.131 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.84%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypohidrotic ectodermal dysplasia

Computational evidence

Protein change
AlphaMissense	0.131	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.61, phastCons 0.18
Regional constraint	o/e 0.83	unconstrained · MANE · 88 kb · p 0.0061 · regional, not allelic
Overall
CADD	21.7	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 3.84% Middle Eastern · 233/6,062 alleles

Filtering AF 3.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.28%

Overall 2.66% 42,989/1,614,052 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.84%	26
European (non-Finnish)	3.09%	32
Finnishnot grpmax-eligible	2.8%	36
Remaining individualsnot grpmax-eligible	2.31%	43
Admixed American	2.22%	45
Ashkenazi Jewishnot grpmax-eligible	1.24%	81
South Asian	1.15%	87
African / African-American	0.472%	212
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00223%	44,870

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.Ser103Phe
Coding: c.308C>T
MANE Select: NM_145861
dbSNP: rs114632254
Type: single nucleotide variant
Location: chr1:236482309 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.81
Residue 103: a UniProt-annotated variant site (in)

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

Disease context

hypohidrotic ectodermal dysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Hypohidrotic ectodermal dysplasia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

EDARADD p.Arg66Ter Pathogenic ★★ same condition
EDARADD c.*863C>T Uncertain significance ★★ same condition
EDARADD p.Arg170Gln Uncertain significance ★★ ⚠ same condition
EDARADD p.Arg196His 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

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-ser103phe (accessed [today's date]).

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