Is ELMOD1 p.Asp245Glu (c.735C>A) pathogenic?

ELMOD1 p.Asp245Glu (c.735C>A) is classified Uncertain significance in ELMOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.3635); Very rare (popmax 0.000767%, nfe).

How common is ELMOD1 p.Asp245Glu (c.735C>A) in the general population?

ELMOD1 p.Asp245Glu (c.735C>A) is very rare (popmax 0.000767%, nfe) (gnomAD).

What do computational predictors say about ELMOD1 p.Asp245Glu (c.735C>A)?

AlphaMissense predicts ambiguous (score 0.3635) — an in-silico prediction, not a clinical call.

ELMOD1 p.Asp245Glu

c.735C>A · VCV4248391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000767%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3635	ambiguous
REVEL	0.24	benign-leaning
SaProt	LLR -7.74	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -3.8
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0031 · regional, not allelic
Overall
CADD	2.815	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 0.000767% European (non-Finnish) · 9/1,173,796 alleles

Filtering AF 0.000361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.00062% 9/1,450,554 alleles · very rare

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.Asp245Glu
Coding: c.735C>A
MANE Select: NM_018712
Type: single nucleotide variant
Location: chr11:107655969 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 90.80
Residue 245: 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-asp245glu (accessed [today's date]).

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