Is EDDM3A p.Ile69Val (c.205A>G) pathogenic?

EDDM3A p.Ile69Val (c.205A>G) is classified Uncertain significance in EDDM3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1102); Very rare (popmax 0.00133%, afr).

How common is EDDM3A p.Ile69Val (c.205A>G) in the general population?

EDDM3A p.Ile69Val (c.205A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about EDDM3A p.Ile69Val (c.205A>G)?

AlphaMissense predicts likely benign (score 0.1102) — an in-silico prediction, not a clinical call.

EDDM3A p.Ile69Val

c.205A>G · VCV3506637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1102	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP -2.3, phastCons 0.002
Regional constraint	o/e 1.12	unconstrained · MANE · 440 bp · p 0.1 · regional, not allelic
Overall
CADD	0.637	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Overall 0.000657% 1/152,178 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: EDDM3A
Protein: p.Ile69Val
Coding: c.205A>G
MANE Select: NM_006683
Type: single nucleotide variant
Location: chr14:20747785 (GRCh38)
Gene constraint: LOEUF 1.943 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 91.64

Full EDDM3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDDM3A p.Arg118Lys Uncertain significance ★ ⚠ same type
EDDM3A p.Arg43Gln Uncertain significance ★ ⚠ same type
EDDM3A p.Arg78Cys Uncertain significance ★ ⚠ same type
EDDM3A p.Asn26Ser Uncertain significance ★ ⚠ same type
EDDM3A p.Asp130Gly Uncertain significance ★ ⚠ same type
EDDM3A p.Cys127Trp Uncertain significance ★ ⚠ same type
EDDM3A p.Cys22Trp Uncertain significance ★ ⚠ same type
EDDM3A p.Cys22Tyr 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/eddm3a-p-ile69val (accessed [today's date]).

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