Is ELMOD1 p.Arg154Trp (c.460C>T) pathogenic?

ELMOD1 p.Arg154Trp (c.460C>T) is classified Uncertain significance in ELMOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.9766); Very rare (popmax 0.00501%, amr).

How common is ELMOD1 p.Arg154Trp (c.460C>T) in the general population?

ELMOD1 p.Arg154Trp (c.460C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about ELMOD1 p.Arg154Trp (c.460C>T)?

AlphaMissense predicts likely pathogenic (score 0.9766) — an in-silico prediction, not a clinical call.

ELMOD1 p.Arg154Trp

c.460C>T · VCV4248387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9766 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9766	likely pathogenic
REVEL	0.611	indeterminate
SaProt	LLR -16.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.031, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0031 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00501% Admixed American · 3/59,940 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,613,028 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,980
European (non-Finnish)	0.000339%	294,894

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: ELMOD1
Protein: p.Arg154Trp
Coding: c.460C>T
MANE Select: NM_018712
Type: single nucleotide variant
Location: chr11:107647507 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.80
Residue 154: the elmo domain

Full ELMOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD1 p.Ala117Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala188Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala221Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala231Pro Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala326Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala76Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg113Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg123Leu 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/elmod1-p-arg154trp (accessed [today's date]).

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