Is ELMOD3 p.Ser344Phe (c.1031C>T) pathogenic?

ELMOD3 p.Ser344Phe (c.1031C>T) is classified Uncertain significance in ELMOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-02). AlphaMissense: likely benign (0.1242); Absent from gnomAD v4.1; Associated with hearing loss, autosomal dominant 81.

What condition is associated with ELMOD3 p.Ser344Phe (c.1031C>T)?

ELMOD3 p.Ser344Phe (c.1031C>T) is associated with hearing loss, autosomal dominant 81 (ClinVar).

How common is ELMOD3 p.Ser344Phe (c.1031C>T) in the general population?

ELMOD3 p.Ser344Phe (c.1031C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELMOD3 p.Ser344Phe (c.1031C>T)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ser344Phe

c.1031C>T · rs2529169535 · VCV2431866

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss, autosomal dominant 81

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -8.53	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 3.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ser344Phe
Coding: c.1031C>T
MANE Select: NM_001135022
dbSNP: rs2529169535
Type: single nucleotide variant
Location: chr2:85390847 (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

Disease context

hearing loss, autosomal dominant 81 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELMOD3 p.Ala234Val Uncertain significance ★★ ⚠ same condition
ELMOD3 c.269-13C>T Benign/Likely benign ★★ same condition
ELMOD3 c.-372+1G>A Uncertain significance ★ same condition
ELMOD3 p.Gly141Arg Uncertain significance ★ ⚠ same condition
ELMOD3 p.His171Arg Uncertain significance ★ ⚠ same condition
ELMOD3 p.Ala289Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala38Thr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Gln100Ter 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-ser344phe (accessed [today's date]).

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