Is ELMOD1 p.His134Pro (c.401A>C) pathogenic?

ELMOD1 p.His134Pro (c.401A>C) is classified Uncertain significance in ELMOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.9854); Very rare (popmax 8.48e-05%, nfe).

How common is ELMOD1 p.His134Pro (c.401A>C) in the general population?

ELMOD1 p.His134Pro (c.401A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ELMOD1 p.His134Pro (c.401A>C)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

ELMOD1 p.His134Pro

c.401A>C · VCV4017588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -17.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0031 · regional, not allelic
Overall
CADD	29.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,780 alleles

Overall 6.2e-05% 1/1,613,808 alleles · very rare exomes 1/1,461,472 · genomes 0/152,336 · joint denominator

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: ELMOD1
Protein: p.His134Pro
Coding: c.401A>C
MANE Select: NM_018712
Type: single nucleotide variant
Location: chr11:107635746 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.80
Residue 134: the elmo domain

Full ELMOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD1 p.Ala117Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala188Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala221Val Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala231Pro Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala326Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Ala76Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg113Thr Uncertain significance ★ ⚠ same type
ELMOD1 p.Arg123Leu 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/elmod1-p-his134pro (accessed [today's date]).

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