Is EDIL3 p.Ile275Val (c.823A>G) pathogenic?

EDIL3 p.Ile275Val (c.823A>G) is classified Likely benign in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.0534); Ultra-rare (popmax 0.0253%, amr).

How common is EDIL3 p.Ile275Val (c.823A>G) in the general population?

EDIL3 p.Ile275Val (c.823A>G) is ultra-rare (popmax 0.0253%, amr) (gnomAD).

What do computational predictors say about EDIL3 p.Ile275Val (c.823A>G)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

EDIL3 p.Ile275Val

c.823A>G · rs199553930 · VCV2350911

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0534	likely benign
REVEL	0.365	indeterminate
SaProt	LLR -6.31	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 1.1	GERP 1, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	10.98	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 0.0253% Admixed American · 15/59,352 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0126%

Overall 0.00621% 100/1,610,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0609%	1,641
Admixed Americangrpmax	0.0253%	3,957
African / African-American	0.00668%	14,961
European (non-Finnish)	0.00339%	29,468
Remaining individualsnot grpmax-eligible	0.0016%	62,342

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile275Val
Coding: c.823A>G
MANE Select: NM_005711
dbSNP: rs199553930
Type: single nucleotide variant
Location: chr5:84064829 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 275: 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-ile275val (accessed [today's date]).

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