Is EDA2R p.Gln110Pro (c.329A>C) pathogenic?

EDA2R p.Gln110Pro (c.329A>C) is classified Uncertain significance in EDA2R (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-13). AlphaMissense: ambiguous (0.5387); Very rare (popmax 0.000335%, nfe).

How common is EDA2R p.Gln110Pro (c.329A>C) in the general population?

EDA2R p.Gln110Pro (c.329A>C) is very rare (popmax 0.000335%, nfe) (gnomAD).

What do computational predictors say about EDA2R p.Gln110Pro (c.329A>C)?

AlphaMissense predicts ambiguous (score 0.5387) — an in-silico prediction, not a clinical call.

EDA2R p.Gln110Pro

c.329A>C · rs769441083 · VCV452543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000335%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5387	ambiguous
REVEL	0.032	moderately benign-leaning
SaProt	LLR -12.38	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.68, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 17 kb · p 0.0014 · regional, not allelic
Overall
CADD	18.42	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 0.000335% European (non-Finnish) · 3/894,263 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000274% 3/1,096,053 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: EDA2R
Protein: p.Gln110Pro
Coding: c.329A>C
MANE Select: NM_021783
dbSNP: rs769441083
Type: single nucleotide variant
Location: chrX:66604444 (GRCh38)
Structure: AlphaFold pLDDT 69.14
Residue 110: a disulfide bond

Full EDA2R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDA2R p.Leu27= Benign ★★ same type
EDA2R p.Pro112Ser Likely benign ★★ ⚠ same type
EDA2R p.Tyr8His Benign ★★ same type
EDA2R p.Ala119Val Uncertain significance ★ ⚠ same type
EDA2R p.Arg14Gln Uncertain significance ★ ⚠ same type
EDA2R p.Arg47Cys Uncertain significance ★ ⚠ same type
EDA2R p.Arg95Cys Uncertain significance ★ ⚠ same type
EDA2R p.Cys15Tyr Uncertain significance ★ ⚠ same type

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/eda2r-p-gln110pro (accessed [today's date]).

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