Is BBC3 p.Gln14Lys (c.40C>A) pathogenic?

BBC3 p.Gln14Lys (c.40C>A) is classified Uncertain significance in BBC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.2613); Very rare (popmax 0.00402%, nfe).

How common is BBC3 p.Gln14Lys (c.40C>A) in the general population?

BBC3 p.Gln14Lys (c.40C>A) is very rare (popmax 0.00402%, nfe) (gnomAD).

What do computational predictors say about BBC3 p.Gln14Lys (c.40C>A)?

AlphaMissense predicts likely benign (score 0.2613) — an in-silico prediction, not a clinical call.

BBC3 p.Gln14Lys

c.40C>A · rs1030402131 · VCV2211520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2613	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.76	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 4	GERP 1, phastCons 1
Overall
CADD	16.03	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

Grpmax group 0.00402% European (non-Finnish) · 46/1,144,214 alleles

Filtering AF 0.00308% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00304% 47/1,548,360 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00402%	24,874
Remaining individualsnot grpmax-eligible	0.00167%	59,956

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: BBC3
Protein: p.Gln14Lys
Coding: c.40C>A
MANE Select: NM_014417 · reported on NM_001127240
dbSNP: rs1030402131
Type: single nucleotide variant
Location: chr19:47232563 (GRCh38)
Gene constraint: LOEUF 1.293 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 47.60 · 13 PDB
Residue 14: 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-gln14lys (accessed [today's date]).

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