Is EDIL3 p.Ala75Ser (c.223G>T) pathogenic?

EDIL3 p.Ala75Ser (c.223G>T) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.0662); Very rare (popmax 8.54e-05%, nfe).

How common is EDIL3 p.Ala75Ser (c.223G>T) in the general population?

EDIL3 p.Ala75Ser (c.223G>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about EDIL3 p.Ala75Ser (c.223G>T)?

AlphaMissense predicts likely benign (score 0.0662) — an in-silico prediction, not a clinical call.

EDIL3 p.Ala75Ser

c.223G>T · rs763672716 · VCV2308078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0662	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -5.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.55	GERP 0.45, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	14.93	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 8.54e-05% European (non-Finnish) · 1/1,171,618 alleles

Overall 6.26e-05% 1/1,598,528 alleles · very rare exomes 1/1,448,222 · genomes 0/150,306 · joint denominator

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.Ala75Ser
Coding: c.223G>T
MANE Select: NM_005711
dbSNP: rs763672716
Type: single nucleotide variant
Location: chr5:84229858 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 75: the egf-like 2 domain

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

Similar variants

EDIL3 p.Ala75Thr Uncertain significance ★ ⚠ same residue
EDIL3 p.Ala396Thr Uncertain significance ★ ⚠ same type
EDIL3 p.Ala42Val 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
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-ala75ser (accessed [today's date]).

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