Is EDA2R p.Pro112Ser (c.334C>T) pathogenic?

EDA2R p.Pro112Ser (c.334C>T) is classified Likely benign in EDA2R (ClinVar, Multiple submitters, 5 submitters; last evaluated 2018-12-14). AlphaMissense: likely pathogenic (0.5914); Rare (popmax 0.484%, nfe).

How common is EDA2R p.Pro112Ser (c.334C>T) in the general population?

EDA2R p.Pro112Ser (c.334C>T) is rare (popmax 0.484%, nfe) (gnomAD).

What do computational predictors say about EDA2R p.Pro112Ser (c.334C>T)?

AlphaMissense predicts likely pathogenic (score 0.5914) — an in-silico prediction, not a clinical call.

EDA2R p.Pro112Ser

c.334C>T · rs12837393 · VCV718792

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.5914 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.484%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5914	likely pathogenic
REVEL	0.176	moderately benign-leaning
SaProt	LLR -10.45	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.68, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 17 kb · p 0.0014 · regional, not allelic
Overall
CADD	22.3	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 0.484% European (non-Finnish) · 4,323/893,446 alleles

Filtering AF 0.472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.467%

Overall 0.387% 4,674/1,206,820 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.574%	174
European (non-Finnish)grpmax	0.484%	207
Remaining individualsnot grpmax-eligible	0.246%	406
Middle Eastern	0.0923%	1,084
Admixed American	0.0787%	1,270
Finnishnot grpmax-eligible	0.0731%	1,367
African / African-American	0.0474%	2,112
South Asian	0.0125%	8,008

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro112Ser
Coding: c.334C>T
MANE Select: NM_021783
dbSNP: rs12837393
Type: single nucleotide variant
Location: chrX:66604439 (GRCh38)
Structure: AlphaFold pLDDT 69.14
Residue 112: 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.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
EDA2R p.Cys162Gly 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-pro112ser (accessed [today's date]).

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