Is BBC3 p.Gln121= (c.363G>A) pathogenic?

BBC3 p.Gln121= (c.363G>A) is classified Uncertain significance in BBC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1181); Absent from gnomAD v4.1.

How common is BBC3 p.Gln121= (c.363G>A) in the general population?

BBC3 p.Gln121= (c.363G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBC3 p.Gln121= (c.363G>A)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

BBC3 p.Gln121=

c.363G>A · VCV3990066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.38	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 -0.2	GERP 2, phastCons 0.46
Overall
CADD	6.747	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

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: BBC3
Protein: p.Gln121=
Coding: c.363G>A
MANE Select: NM_014417
Type: single nucleotide variant
Location: chr19:47226666 (GRCh38)
Gene constraint: LOEUF 1.293 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 47.60 · 13 PDB
Residue 121: the 'disordered' region

Full BBC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBC3 c.*23C>T Benign/Likely benign ★★ same type
BBC3 c.-3G>A Uncertain significance ★ ⚠ same type
BBC3 c.*16C>T Uncertain significance ★ ⚠ same type
BBC3 c.*46C>T Uncertain significance ★ ⚠ same type
BBC3 c.*57C>T Uncertain significance ★ ⚠ same type
BBC3 c.*64C>G Uncertain significance ★ ⚠ same type
BBC3 c.*76C>G Uncertain significance ★ ⚠ same type
BBC3 c.*79G>T 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/bbc3-p-gln121 (accessed [today's date]).

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