Is BMAL2 p.His409Gln (c.1227T>G) pathogenic?

BMAL2 p.His409Gln (c.1227T>G) is classified Uncertain significance in BMAL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely pathogenic (0.649); Absent from gnomAD v4.1.

How common is BMAL2 p.His409Gln (c.1227T>G) in the general population?

BMAL2 p.His409Gln (c.1227T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BMAL2 p.His409Gln (c.1227T>G)?

AlphaMissense predicts likely pathogenic (score 0.649) — an in-silico prediction, not a clinical call.

BMAL2 p.His409Gln

c.1227T>G · rs2539904162 · VCV3134467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.649 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.649	likely pathogenic
REVEL	0.688	pathogenic-leaning
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -0.59, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 87 kb · p 0.025 · regional, not allelic
Overall
CADD	21.5	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: BMAL2
Protein: p.His409Gln
Coding: c.1227T>G
MANE Select: NM_020183
dbSNP: rs2539904162
Type: single nucleotide variant
Location: chr12:27401323 (GRCh38)
Structure: AlphaFold pLDDT 61.96 · 1 PDB
Residue 409: the pas 2 domain

Full BMAL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMAL2 p.Ala141Val Uncertain significance ★ ⚠ same type
BMAL2 p.Ala388Thr Uncertain significance ★ ⚠ same type
BMAL2 p.Ala3Thr Uncertain significance ★ ⚠ same type
BMAL2 p.Ala583Thr Uncertain significance ★ ⚠ same type
BMAL2 p.Arg118Gln Uncertain significance ★ ⚠ same type
BMAL2 p.Arg118Trp Uncertain significance ★ ⚠ same type
BMAL2 p.Arg142His Uncertain significance ★ ⚠ same type
BMAL2 p.Arg173Ile 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/bmal2-p-his409gln (accessed [today's date]).

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