Is BMAL1 p.Ala359Pro (c.1075G>C) pathogenic?

BMAL1 p.Ala359Pro (c.1075G>C) is classified Uncertain significance in BMAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-07). AlphaMissense: likely pathogenic (0.7863); Absent from gnomAD v4.1.

How common is BMAL1 p.Ala359Pro (c.1075G>C) in the general population?

BMAL1 p.Ala359Pro (c.1075G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMAL1 p.Ala359Pro (c.1075G>C)?

AlphaMissense predicts likely pathogenic (score 0.7863) — an in-silico prediction, not a clinical call.

BMAL1 p.Ala359Pro

c.1075G>C · VCV4975950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7863 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7863	likely pathogenic
REVEL	0.333	indeterminate
SaProt	LLR -4.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 8,576 bp · p 1.1e-07 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BMAL1
Protein: p.Ala359Pro
Coding: c.1075G>C
MANE Select: NM_001297719
Type: single nucleotide variant
Location: chr11:13374102 (GRCh38)
Structure: AlphaFold pLDDT 67.00 · 3 PDB
Residue 359: the pas 2 domain; an α-helix

Full BMAL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMAL1 c.140+7C>T Uncertain significance ★ same type
BMAL1 p.Arg166Ter Uncertain significance ★ same type
BMAL1 p.Arg238Gly Uncertain significance ★ ⚠ same type
BMAL1 p.Arg276Ter Uncertain significance ★ same type
BMAL1 p.Arg343Trp Uncertain significance ★ ⚠ same type
BMAL1 p.Arg37Cys Uncertain significance ★ ⚠ same type
BMAL1 p.Arg497Gln Uncertain significance ★ ⚠ same type
BMAL1 p.Asn181Ser 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/bmal1-p-ala359pro (accessed [today's date]).

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