Is ELMOD3 p.Glu376Lys (c.1126G>A) pathogenic?

ELMOD3 p.Glu376Lys (c.1126G>A) is classified Conflicting classifications of pathogenicity in ELMOD3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-23). AlphaMissense: likely benign (0.066); Ultra-rare (popmax 0.0863%, amr).

How common is ELMOD3 p.Glu376Lys (c.1126G>A) in the general population?

ELMOD3 p.Glu376Lys (c.1126G>A) is ultra-rare (popmax 0.0863%, amr) (gnomAD).

What do computational predictors say about ELMOD3 p.Glu376Lys (c.1126G>A)?

AlphaMissense predicts likely benign (score 0.066) — an in-silico prediction, not a clinical call.

ELMOD3 p.Glu376Lys

c.1126G>A · rs564403550 · VCV1318159

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0863%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.066	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.60	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 0.47	GERP -4.3, phastCons 0.02
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	13.01	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 0.0863% Admixed American · 44/51,004 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0589%

Overall 0.00928% 144/1,551,650 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0863%	1,159
East Asian	0.0318%	3,146
South Asian	0.0202%	4,944
Middle Eastern	0.0167%	5,990
African / African-American	0.0082%	12,191
Remaining individualsnot grpmax-eligible	0.00665%	15,038
European (non-Finnish)	0.00497%	20,122
Finnishnot grpmax-eligible	0.00334%	29,950

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.Glu376Lys
Coding: c.1126G>A
MANE Select: NM_001135022
dbSNP: rs564403550
Type: single nucleotide variant
Location: chr2:85390942 (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

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-glu376lys (accessed [today's date]).

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