Is EDAR p.Gly161Ser (c.481G>A) pathogenic?

EDAR p.Gly161Ser (c.481G>A) is classified Conflicting classifications of pathogenicity in EDAR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-02). AlphaMissense: likely benign (0.0575); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EDAR p.Gly161Ser (c.481G>A)?

EDAR p.Gly161Ser (c.481G>A) is associated with Inborn genetic diseases (ClinVar).

How common is EDAR p.Gly161Ser (c.481G>A) in the general population?

EDAR p.Gly161Ser (c.481G>A) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about EDAR p.Gly161Ser (c.481G>A)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

EDAR p.Gly161Ser

c.481G>A · rs1553445966 · VCV439636

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -4.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 34 kb · p 0.0061 · regional, not allelic
Overall
CADD	7.745	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 0.00102% European (non-Finnish) · 12/1,175,216 alleles

Filtering AF 0.000545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000827% 12/1,450,658 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.Gly161Ser
Coding: c.481G>A
MANE Select: NM_006267 · reported on NM_022336
dbSNP: rs1553445966
Type: single nucleotide variant
Location: chr2:108912726 (GRCh38)

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

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-gly161ser (accessed [today's date]).

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