Is EDIL3 p.Val402Ala (c.1205T>C) pathogenic?

EDIL3 p.Val402Ala (c.1205T>C) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: ambiguous (0.4235); Ultra-rare (popmax 0.0224%, eas).

How common is EDIL3 p.Val402Ala (c.1205T>C) in the general population?

EDIL3 p.Val402Ala (c.1205T>C) is ultra-rare (popmax 0.0224%, eas) (gnomAD).

What do computational predictors say about EDIL3 p.Val402Ala (c.1205T>C)?

AlphaMissense predicts ambiguous (score 0.4235) — an in-silico prediction, not a clinical call.

EDIL3 p.Val402Ala

c.1205T>C · rs771688663 · VCV2491606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4235	ambiguous
REVEL	0.691	pathogenic-leaning
SaProt	LLR -2.48	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	25.2	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 0.0224% East Asian · 10/44,614 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00921%

Overall 0.000621% 10/1,610,518 alleles · ultra-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: EDIL3
Protein: p.Val402Ala
Coding: c.1205T>C
MANE Select: NM_005711
dbSNP: rs771688663
Type: single nucleotide variant
Location: chr5:83963293 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 402: a disulfide bond; the f5/8 type c 2 domain

Full EDIL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EDIL3 p.Ala396Thr Uncertain significance ★ ⚠ same type
EDIL3 p.Ala42Val Uncertain significance ★ ⚠ same type
EDIL3 p.Ala75Ser Uncertain significance ★ ⚠ same type
EDIL3 p.Ala75Thr Uncertain significance ★ ⚠ same type
EDIL3 p.Arg181Gln Uncertain significance ★ ⚠ same type
EDIL3 p.Arg212Ser Uncertain significance ★ ⚠ same type
EDIL3 p.Arg272Cys Uncertain significance ★ ⚠ same type
EDIL3 p.Arg272His 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/edil3-p-val402ala (accessed [today's date]).

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