Is ELMO2 p.Pro81Ala (c.241C>G) pathogenic?

ELMO2 p.Pro81Ala (c.241C>G) is classified Uncertain significance in ELMO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.3124); Very rare (popmax 0.00839%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ELMO2 p.Pro81Ala (c.241C>G)?

ELMO2 p.Pro81Ala (c.241C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ELMO2 p.Pro81Ala (c.241C>G) in the general population?

ELMO2 p.Pro81Ala (c.241C>G) is very rare (popmax 0.00839%, nfe) (gnomAD).

What do computational predictors say about ELMO2 p.Pro81Ala (c.241C>G)?

AlphaMissense predicts likely benign (score 0.3124) — an in-silico prediction, not a clinical call.

ELMO2 p.Pro81Ala

c.241C>G · VCV4618433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00839%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3124	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -8.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 27 kb · p 2.6e-31 · regional, not allelic
Overall
CADD	26.3	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 0.00839% European (non-Finnish) · 99/1,179,778 alleles

Filtering AF 0.00702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00644% 104/1,613,734 alleles · very rare exomes 101/1,461,552 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00839%	11,917
African / African-American	0.00401%	24,968
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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: ELMO2
Protein: p.Pro81Ala
Coding: c.241C>G
MANE Select: NM_133171
Type: single nucleotide variant
Location: chr20:46393095 (GRCh38)
Gene constraint: LOEUF 0.486 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 88.96 · 2 PDB
Residue 81: an α-helix

Full ELMO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELMO2 p.Pro81Leu Uncertain significance ★ ⚠ same residue
ELMO2 p.Asn490Lys Uncertain significance ★★ ⚠ same condition
ELMO2 p.Glu468Asp Uncertain significance ★★ ⚠ same condition
ELMO2 p.Ser396Gly Uncertain significance ★★ ⚠ same condition
ELMO2 p.Thr482Ala Uncertain significance ★★ ⚠ same condition
ELMO2 p.Ala235Thr Uncertain significance ★ ⚠ same condition
ELMO2 p.Ala246Ser Uncertain significance ★ ⚠ same condition
ELMO2 p.Ala333Gly Uncertain significance ★ ⚠ same condition

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/elmo2-p-pro81ala (accessed [today's date]).

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