Is ELMOD3 p.Ser254Phe (c.761C>T) pathogenic?

ELMOD3 p.Ser254Phe (c.761C>T) is classified Uncertain significance in ELMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: likely pathogenic (0.9316); Absent from gnomAD v4.1.

How common is ELMOD3 p.Ser254Phe (c.761C>T) in the general population?

ELMOD3 p.Ser254Phe (c.761C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELMOD3 p.Ser254Phe (c.761C>T)?

AlphaMissense predicts likely pathogenic (score 0.9316) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ser254Phe

c.761C>T · rs2529145993 · VCV2314382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9316 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9316	likely pathogenic · top 3% in ELMOD3
REVEL	0.446	indeterminate
SaProt	LLR -14.41	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	26.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELMOD3
Protein: p.Ser254Phe
Coding: c.761C>T
MANE Select: NM_001135022
dbSNP: rs2529145993
Type: single nucleotide variant
Location: chr2:85389773 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18
Residue 254: 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-ser254phe (accessed [today's date]).

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