Is ELMOD3 p.Ala234Val (c.701C>T) pathogenic?

ELMOD3 p.Ala234Val (c.701C>T) is classified Uncertain significance in ELMOD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-19). AlphaMissense: likely benign (0.2433); Very rare (popmax 0.00222%, sas); Associated with hearing loss, autosomal dominant 81.

What condition is associated with ELMOD3 p.Ala234Val (c.701C>T)?

ELMOD3 p.Ala234Val (c.701C>T) is associated with hearing loss, autosomal dominant 81, autosomal recessive nonsyndromic hearing loss 88 (ClinVar).

How common is ELMOD3 p.Ala234Val (c.701C>T) in the general population?

ELMOD3 p.Ala234Val (c.701C>T) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about ELMOD3 p.Ala234Val (c.701C>T)?

AlphaMissense predicts likely benign (score 0.2433) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ala234Val

c.701C>T · rs779560360 · VCV1407696

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hearing loss, autosomal dominant 81

Computational evidence

Protein change
AlphaMissense	0.2433	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	29.1	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 0.00222% South Asian · 2/90,216 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000994% 16/1,609,456 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00222%	45,108
Admixed American	0.00168%	59,456
Finnishnot grpmax-eligible	0.00156%	64,014
African / African-American	0.00134%	74,608
European (non-Finnish)	0.000934%	107,080

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.Ala234Val
Coding: c.701C>T
MANE Select: NM_001135022
dbSNP: rs779560360
Type: single nucleotide variant
Location: chr2:85377437 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18
Residue 234: the elmo domain

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

Also linked: autosomal recessive nonsyndromic hearing loss 88

Similar variants

ELMOD3 p.Ala234= Likely benign ★★ same residue
ELMOD3 p.Pro143Ala Uncertain significance ★★ ⚠ same condition
ELMOD3 c.269-13C>T Benign/Likely benign ★★ same condition
ELMOD3 p.Leu265Ser Pathogenic ★ 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.Ser344Phe Uncertain significance ★ ⚠ same condition

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-ala234val (accessed [today's date]).

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