Is ELMOD3 p.Ala133Thr (c.397G>A) pathogenic?

ELMOD3 p.Ala133Thr (c.397G>A) is classified Benign/Likely benign in ELMOD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-21). AlphaMissense: likely benign (0.1148); Rare (popmax 0.667%, afr).

How common is ELMOD3 p.Ala133Thr (c.397G>A) in the general population?

ELMOD3 p.Ala133Thr (c.397G>A) is rare (popmax 0.667%, afr) (gnomAD).

What do computational predictors say about ELMOD3 p.Ala133Thr (c.397G>A)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ala133Thr

c.397G>A · rs145555897 · VCV1268898

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.52, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	19.48	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 0.667% African / African-American · 501/75,058 alleles

Filtering AF 0.619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.6%

Overall 0.038% 614/1,614,148 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.667%	150
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Middle Eastern	0.033%	3,030
Admixed American	0.0267%	3,752
East Asian	0.0134%	7,481
Finnishnot grpmax-eligible	0.0109%	9,147
South Asian	0.00988%	10,121
European (non-Finnish)	0.00347%	28,780

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.Ala133Thr
Coding: c.397G>A
MANE Select: NM_001135022
dbSNP: rs145555897
Type: single nucleotide variant
Location: chr2:85371122 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18

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

Similar variants

ELMOD3 p.Ala133= Likely benign ★★ same residue
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

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-ala133thr (accessed [today's date]).

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