Is ELMO1 p.Glu306Gln (c.916G>C) pathogenic?

ELMO1 p.Glu306Gln (c.916G>C) is classified Uncertain significance in ELMO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.7085); Very rare (popmax 0.00161%, nfe).

How common is ELMO1 p.Glu306Gln (c.916G>C) in the general population?

ELMO1 p.Glu306Gln (c.916G>C) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about ELMO1 p.Glu306Gln (c.916G>C)?

AlphaMissense predicts likely pathogenic (score 0.7085) — an in-silico prediction, not a clinical call.

ELMO1 p.Glu306Gln

c.916G>C · VCV4248347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7085	likely pathogenic
REVEL	0.411	indeterminate
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 378 kb · p 6.4e-17 · regional, not allelic
Overall
CADD	29.6	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 0.00161% European (non-Finnish) · 19/1,179,728 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 21/1,612,744 alleles · very rare exomes 19/1,460,604 · genomes 2/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,091
Remaining individualsnot grpmax-eligible	0.0016%	62,378
African / African-American	0.00134%	74,864

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.Glu306Gln
Coding: c.916G>C
MANE Select: NM_014800
Type: single nucleotide variant
Location: chr7:37213373 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.95 · 18 PDB

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-glu306gln (accessed [today's date]).

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