Is ELMOD2 p.Val115Glu (c.344T>A) pathogenic?

ELMOD2 p.Val115Glu (c.344T>A) is classified Uncertain significance in ELMOD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-04). AlphaMissense: likely benign (0.1342); Very rare (popmax 0.00818%, afr).

How common is ELMOD2 p.Val115Glu (c.344T>A) in the general population?

ELMOD2 p.Val115Glu (c.344T>A) is very rare (popmax 0.00818%, afr) (gnomAD).

What do computational predictors say about ELMOD2 p.Val115Glu (c.344T>A)?

AlphaMissense predicts likely benign (score 0.1342) — an in-silico prediction, not a clinical call.

ELMOD2 p.Val115Glu

c.344T>A · rs369960970 · VCV2211955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00818%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1342	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -5.83	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 6.4	GERP 0.25, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.59 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.00818% African / African-American · 6/73,354 alleles

Filtering AF 0.00353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000818% 13/1,589,506 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00818%	12,226
Remaining individualsnot grpmax-eligible	0.00812%	12,310
South Asian	0.00117%	85,806
European (non-Finnish)	8.55e-05%	1,170,074

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: ELMOD2
Protein: p.Val115Glu
Coding: c.344T>A
MANE Select: NM_153702
dbSNP: rs369960970
Type: single nucleotide variant
Location: chr4:140537486 (GRCh38)
Gene constraint: LOEUF 0.881 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.39

Full ELMOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD2 p.Val115Leu Uncertain significance ★ ⚠ same residue
ELMOD2 c.142+43G>T Benign ★★ same type
ELMOD2 c.270-81T>G Benign ★★ same type
ELMOD2 c.-9-294A>G Benign ★★ same type
ELMOD2 c.*9C>T Benign/Likely benign ★★ same type
ELMOD2 p.Lys143Thr Benign/Likely benign ★★ same type
ELMOD2 p.Val39Gly Likely benign ★★ same type
ELMOD2 p.Arg167Ser 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/elmod2-p-val115glu (accessed [today's date]).

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