Is ELMOD3 p.Arg325Trp (c.973C>T) pathogenic?

ELMOD3 p.Arg325Trp (c.973C>T) is classified Uncertain significance in ELMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-26). AlphaMissense: likely benign (0.1679); Ultra-rare (popmax 0.0169%, mid).

How common is ELMOD3 p.Arg325Trp (c.973C>T) in the general population?

ELMOD3 p.Arg325Trp (c.973C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about ELMOD3 p.Arg325Trp (c.973C>T)?

AlphaMissense predicts likely benign (score 0.1679) — an in-silico prediction, not a clinical call.

ELMOD3 p.Arg325Trp

c.973C>T · VCV3709717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1679 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1679	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 0.025
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	21.9	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 0.0169% Middle Eastern · 1/5,906 alleles

Filtering AF 0.00632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0059%

Overall 0.00606% 94/1,551,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,906
European (non-Finnish)	0.00767%	13,034
Admixed American	0.00588%	16,995
Remaining individualsnot grpmax-eligible	0.00333%	30,039

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.Arg325Trp
Coding: c.973C>T
MANE Select: NM_001135022
Type: single nucleotide variant
Location: chr2:85390789 (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.Arg325Leu Benign ★★ ⚠ same residue
ELMOD3 p.Arg325Gln Uncertain significance ★ ⚠ 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

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-arg325trp (accessed [today's date]).

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