Is BMAL1 p.Arg166Ter (c.496C>T) pathogenic?

BMAL1 p.Arg166Ter (c.496C>T) is classified Uncertain significance in BMAL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). Absent from gnomAD v4.1.

How common is BMAL1 p.Arg166Ter (c.496C>T) in the general population?

BMAL1 p.Arg166Ter (c.496C>T) is absent from gnomAD v4.1 (gnomAD).

BMAL1 p.Arg166Ter

c.496C>T · VCV4976010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 20
Splicing
SpliceAI	Δ0.48	acceptor loss, 36 bp away · masked 0 · deltas
Pangolin	Δ0.42	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.8, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg166Ter
Coding: c.496C>T
MANE Select: NM_001297719
Type: single nucleotide variant
Location: chr11:13365536 (GRCh38)
Structure: AlphaFold pLDDT 67.00 · 3 PDB
Residue 166: the pas 1 domain

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.Ala359Pro 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-arg166ter (accessed [today's date]).

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