Is EDA p.Arg65Gly (c.193C>G) pathogenic?

EDA p.Arg65Gly (c.193C>G) is classified Pathogenic in EDA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-01-01). AlphaMissense: likely pathogenic (0.8109); Absent from gnomAD v4.1; Associated with tooth agenesis, selective, X-linked, 1.

What condition is associated with EDA p.Arg65Gly (c.193C>G)?

EDA p.Arg65Gly (c.193C>G) is associated with tooth agenesis, selective, X-linked, 1 (ClinVar).

How common is EDA p.Arg65Gly (c.193C>G) in the general population?

EDA p.Arg65Gly (c.193C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Arg65Gly (c.193C>G)?

AlphaMissense predicts likely pathogenic (score 0.8109) — an in-silico prediction, not a clinical call.

EDA p.Arg65Gly

c.193C>G · rs132630319 · VCV11044

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8109 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tooth agenesis, selective, X-linked, 1

Computational evidence

Protein change
AlphaMissense	0.8109	likely pathogenic ✓ concordant with ClinVar
REVEL	0.872	moderately pathogenic-leaning
SaProt	LLR -11.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.22, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EDA
Protein: p.Arg65Gly
Coding: c.193C>G
MANE Select: NM_001399
dbSNP: rs132630319
Type: single nucleotide variant
Location: chrX:69616501 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 65: a UniProt-annotated variant site (in sthagx1)

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

Disease context

tooth agenesis, selective, X-linked, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDA p.Arg65= Likely benign ★ same residue
EDA p.Arg155Cys Pathogenic ★★ ⚠ same condition
EDA p.Arg156Cys Pathogenic/Likely pathogenic ★★ same condition
EDA p.Arg156His Pathogenic ★★ ⚠ same condition
EDA p.Arg289Cys Pathogenic ★★ same condition
EDA p.Arg289His Pathogenic/Likely pathogenic ★★ ⚠ same condition
EDA p.Gly299Ser Pathogenic/Likely pathogenic ★★ same condition
EDA p.Met1Thr Pathogenic ★★ 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/eda-p-arg65gly (accessed [today's date]).

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