Is ELMO3 p.Cys444Arg (c.1330T>C) pathogenic?

ELMO3 p.Cys444Arg (c.1330T>C) is classified Uncertain significance in ELMO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely pathogenic (0.862); Absent from gnomAD v4.1.

How common is ELMO3 p.Cys444Arg (c.1330T>C) in the general population?

ELMO3 p.Cys444Arg (c.1330T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELMO3 p.Cys444Arg (c.1330T>C)?

AlphaMissense predicts likely pathogenic (score 0.862) — an in-silico prediction, not a clinical call.

ELMO3 p.Cys444Arg

c.1330T>C · VCV3507988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.862	likely pathogenic
REVEL	0.695	pathogenic-leaning
SaProt	LLR -10.01	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 6.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,547 bp · p 0.66 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELMO3
Protein: p.Cys444Arg
Coding: c.1330T>C
MANE Select: NM_024712
Type: single nucleotide variant
Location: chr16:67202465 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04
Residue 444: the elmo domain

Full ELMO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMO3 p.Cys444Tyr Uncertain significance ★ ⚠ same residue
ELMO3 p.Val284Ile Likely benign ★★ ⚠ same type
ELMO3 c.1780+1G>A Uncertain significance ★ same type
ELMO3 c.-11C>T Uncertain significance ★ same type
ELMO3 c.-123A>G Uncertain significance ★ same type
ELMO3 c.-14G>T Uncertain significance ★ same type
ELMO3 c.-28G>C Uncertain significance ★ same type
ELMO3 c.-50G>A 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/elmo3-p-cys444arg (accessed [today's date]).

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