Is EDIL3 p.Arg272His (c.815G>A) pathogenic?

EDIL3 p.Arg272His (c.815G>A) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.0301%, sas).

How common is EDIL3 p.Arg272His (c.815G>A) in the general population?

EDIL3 p.Arg272His (c.815G>A) is ultra-rare (popmax 0.0301%, sas) (gnomAD).

What do computational predictors say about EDIL3 p.Arg272His (c.815G>A)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

EDIL3 p.Arg272His

c.815G>A · VCV4663061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0301%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 1.1, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	17.43	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 0.0301% South Asian · 27/89,734 alleles

Filtering AF 0.0211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00311% 50/1,608,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0301%	3,323
Remaining individualsnot grpmax-eligible	0.00803%	12,451
African / African-American	0.00267%	37,404
East Asian	0.00223%	44,786
European (non-Finnish)	0.00127%	78,519

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.Arg272His
Coding: c.815G>A
MANE Select: NM_005711
Type: single nucleotide variant
Location: chr5:84064837 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 272: 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.Arg272Cys Uncertain significance ★ ⚠ same residue
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.Arg308Gly 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-arg272his (accessed [today's date]).

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