Is ELMO3 p.Arg336Cys (c.1006C>T) pathogenic?

ELMO3 p.Arg336Cys (c.1006C>T) is classified Uncertain significance in ELMO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: ambiguous (0.5146); Very rare (popmax 0.00439%, sas).

How common is ELMO3 p.Arg336Cys (c.1006C>T) in the general population?

ELMO3 p.Arg336Cys (c.1006C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ELMO3 p.Arg336Cys (c.1006C>T)?

AlphaMissense predicts ambiguous (score 0.5146) — an in-silico prediction, not a clinical call.

ELMO3 p.Arg336Cys

c.1006C>T · rs572778974 · VCV3088339

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Computational evidence

Protein change
AlphaMissense	0.5146	ambiguous
REVEL	0.448	indeterminate
SaProt	LLR -7.17	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.62, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,547 bp · p 0.66 · regional, not allelic
Overall
CADD	26.7	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 0.00439% South Asian · 4/91,050 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.0023% 37/1,611,574 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,763
Admixed American	0.00334%	29,984
European (non-Finnish)	0.00263%	38,060

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: ELMO3
Protein: p.Arg336Cys
Coding: c.1006C>T
MANE Select: NM_024712
dbSNP: rs572778974
Type: single nucleotide variant
Location: chr16:67201829 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04
Residue 336: the elmo domain

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

Similar variants

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
ELMO3 c.-77G>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-arg336cys (accessed [today's date]).

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