Is ELMOD3 p.Ala290Thr (c.868G>A) pathogenic?

ELMOD3 p.Ala290Thr (c.868G>A) is classified Uncertain significance in ELMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.5897); Ultra-rare (popmax 0.0329%, mid).

How common is ELMOD3 p.Ala290Thr (c.868G>A) in the general population?

ELMOD3 p.Ala290Thr (c.868G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ELMOD3 p.Ala290Thr (c.868G>A)?

AlphaMissense predicts likely pathogenic (score 0.5897) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ala290Thr

c.868G>A · rs770248019 · VCV2181169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5897	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -11.85	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	27.9	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

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00316% 51/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0048%	20,829
South Asian	0.00439%	22,773
European (non-Finnish)	0.00305%	32,779

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: ELMOD3
Protein: p.Ala290Thr
Coding: c.868G>A
MANE Select: NM_001135022
dbSNP: rs770248019
Type: single nucleotide variant
Location: chr2:85390190 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18
Residue 290: the elmo domain

Full ELMOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD3 p.Ala234Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala289Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala38Thr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Gln100Ter Uncertain significance ★★ same type
ELMOD3 p.Gln371Ter Uncertain significance ★★ same type
ELMOD3 p.His294Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.His297Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Leu164Met 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/elmod3-p-ala290thr (accessed [today's date]).

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