Is ELMO1 p.Pro609Ser (c.1825C>T) pathogenic?

ELMO1 p.Pro609Ser (c.1825C>T) is classified Uncertain significance in ELMO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.3235); Very rare (popmax 0.00167%, amr).

How common is ELMO1 p.Pro609Ser (c.1825C>T) in the general population?

ELMO1 p.Pro609Ser (c.1825C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ELMO1 p.Pro609Ser (c.1825C>T)?

AlphaMissense predicts likely benign (score 0.3235) — an in-silico prediction, not a clinical call.

ELMO1 p.Pro609Ser

c.1825C>T · rs761554084 · VCV2313975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3235 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3235	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -7.67	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 378 kb · p 6.4e-17 · regional, not allelic
Overall
CADD	25.5	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 0.00167% Admixed American · 1/59,774 alleles

Overall 6.2e-05% 1/1,613,118 alleles · very rare exomes 1/1,460,886 · genomes 0/152,232 · joint denominator

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: ELMO1
Protein: p.Pro609Ser
Coding: c.1825C>T
MANE Select: NM_014800
dbSNP: rs761554084
Type: single nucleotide variant
Location: chr7:36870473 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.95 · 18 PDB
Residue 609: the ph domain; a β-strand

Full ELMO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMO1 p.Ala179Val Uncertain significance ★ ⚠ same type
ELMO1 p.Ala249Gly Uncertain significance ★ ⚠ same type
ELMO1 p.Ala263Val Uncertain significance ★ ⚠ same type
ELMO1 p.Ala99Val Uncertain significance ★ ⚠ same type
ELMO1 p.Arg272Leu Uncertain significance ★ ⚠ same type
ELMO1 p.Arg328Leu Uncertain significance ★ ⚠ same type
ELMO1 p.Arg348His Uncertain significance ★ ⚠ same type
ELMO1 p.Arg415His 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/elmo1-p-pro609ser (accessed [today's date]).

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