Is ELMO3 p.Cys715Phe (c.2144G>T) pathogenic?

ELMO3 p.Cys715Phe (c.2144G>T) is classified Uncertain significance in ELMO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.0851); Ultra-rare (popmax 0.0316%, eas).

How common is ELMO3 p.Cys715Phe (c.2144G>T) in the general population?

ELMO3 p.Cys715Phe (c.2144G>T) is ultra-rare (popmax 0.0316%, eas) (gnomAD).

What do computational predictors say about ELMO3 p.Cys715Phe (c.2144G>T)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

ELMO3 p.Cys715Phe

c.2144G>T · rs561688262 · VCV2518365

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0316%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -3.76	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 5.5	GERP 0.92, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,547 bp · p 0.66 · regional, not allelic
Overall
CADD	16.29	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0316% East Asian · 14/44,360 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.000881% 14/1,588,648 alleles · ultra-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: ELMO3
Protein: p.Cys715Phe
Coding: c.2144G>T
MANE Select: NM_024712
dbSNP: rs561688262
Type: single nucleotide variant
Location: chr16:67203858 (GRCh38)
Gene constraint: LOEUF 1.093 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04

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-cys715phe (accessed [today's date]).

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