Is EDIL3 p.His304Arg (c.911A>G) pathogenic?

EDIL3 p.His304Arg (c.911A>G) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: ambiguous (0.4949); Absent from gnomAD v4.1.

How common is EDIL3 p.His304Arg (c.911A>G) in the general population?

EDIL3 p.His304Arg (c.911A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EDIL3 p.His304Arg (c.911A>G)?

AlphaMissense predicts ambiguous (score 0.4949) — an in-silico prediction, not a clinical call.

EDIL3 p.His304Arg

c.911A>G · rs750012243 · VCV2455483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4949 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4949	ambiguous
REVEL	0.69	pathogenic-leaning
SaProt	LLR -9.89	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 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	22.9	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: EDIL3
Protein: p.His304Arg
Coding: c.911A>G
MANE Select: NM_005711
dbSNP: rs750012243
Type: single nucleotide variant
Location: chr5:84064741 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 304: a disulfide bond; the f5/8 type c 1 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-his304arg (accessed [today's date]).

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