Is EDA p.Leu293Arg (c.878T>G) pathogenic?

EDA p.Leu293Arg (c.878T>G) is classified Pathogenic in EDA (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with tooth agenesis, selective, 2.

What condition is associated with EDA p.Leu293Arg (c.878T>G)?

EDA p.Leu293Arg (c.878T>G) is associated with tooth agenesis, selective, 2 (ClinVar).

How common is EDA p.Leu293Arg (c.878T>G) in the general population?

EDA p.Leu293Arg (c.878T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDA p.Leu293Arg (c.878T>G)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

EDA p.Leu293Arg

c.878T>G · rs2520343370 · VCV2504639

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

tooth agenesis, selective, 2

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic ✓ concordant with ClinVar · top 5% in EDA
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -17.43	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 6.2	GERP 4.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 419 kb · p 2e-10 · regional, not allelic
Overall
CADD	33.0	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.Leu293Arg
Coding: c.878T>G
MANE Select: NM_001399
dbSNP: rs2520343370
Type: single nucleotide variant
Location: chrX:70033482 (GRCh38)
Structure: AlphaFold pLDDT 70.59 · 3 PDB
Residue 293: a β-strand; the thd domain; a UniProt-annotated variant site (in xhed)

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

Disease context

tooth agenesis, selective, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EDA p.Leu293= Benign ★ same residue
EDA c.526+2T>C Pathogenic/Likely pathogenic ★★ same type
EDA c.526+5G>T Likely pathogenic ★★ same type
EDA c.527-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.706+1G>A Pathogenic/Likely pathogenic ★★ same type
EDA c.707-13T>G Pathogenic ★★ same type
EDA c.742-2A>G Pathogenic/Likely pathogenic ★★ same type
EDA c.924+1G>T Likely pathogenic ★★ 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/eda-p-leu293arg (accessed [today's date]).

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