Is EDIL3 p.Thr286Pro (c.856A>C) pathogenic?

EDIL3 p.Thr286Pro (c.856A>C) is classified Uncertain significance in EDIL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.1446); Very rare (popmax 0.00167%, amr).

How common is EDIL3 p.Thr286Pro (c.856A>C) in the general population?

EDIL3 p.Thr286Pro (c.856A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EDIL3 p.Thr286Pro (c.856A>C)?

AlphaMissense predicts likely benign (score 0.1446) — an in-silico prediction, not a clinical call.

EDIL3 p.Thr286Pro

c.856A>C · VCV3506688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1446	likely benign
REVEL	0.71	pathogenic-leaning
SaProt	LLR -8.41	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 421 kb · p 0.21 · regional, not allelic
Overall
CADD	29.3	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 0.00167% Admixed American · 1/59,986 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,613,790 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,986
European (non-Finnish)	0.00136%	73,740

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.Thr286Pro
Coding: c.856A>C
MANE Select: NM_005711
Type: single nucleotide variant
Location: chr5:84064796 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.04 · 1 PDB
Residue 286: 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-thr286pro (accessed [today's date]).

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