Is EDAR p.Ser268= (c.804C>T) pathogenic?

EDAR p.Ser268= (c.804C>T) is classified Likely benign in EDAR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Very rare (popmax 0.00535%, afr); Associated with Inborn genetic diseases.

What condition is associated with EDAR p.Ser268= (c.804C>T)?

EDAR p.Ser268= (c.804C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EDAR p.Ser268= (c.804C>T) in the general population?

EDAR p.Ser268= (c.804C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

EDAR p.Ser268=

c.804C>T · VCV4016148

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -5.5
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,778 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00137% 22/1,607,098 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,694
Remaining individualsnot grpmax-eligible	0.00322%	31,103
South Asian	0.0022%	45,410
Finnishnot grpmax-eligible	0.00158%	63,446
European (non-Finnish)	0.00111%	90,378

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.Ser268=
Coding: c.804C>T
MANE Select: NM_022336
Type: single nucleotide variant
Location: chr2:108908019 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 1 PDB
Residue 268: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDAR p.Ser268Cys Uncertain significance ★★ ⚠ same residue
EDAR p.Ala26Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDAR p.Glu35Lys Uncertain significance ★★ ⚠ same condition
EDAR p.Gly321Arg Uncertain significance ★★ ⚠ same condition
EDAR p.Ala174Val Uncertain significance ★ ⚠ same condition
EDAR p.Ala217Ser Uncertain significance ★ ⚠ same condition
EDAR p.Ala260Val Uncertain significance ★ ⚠ same condition
EDAR p.Ala423Thr Uncertain significance ★ ⚠ 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-ser268 (accessed [today's date]).

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