Is BBC3 p.His103Gln (c.309C>G) pathogenic?

BBC3 p.His103Gln (c.309C>G) is classified Uncertain significance in BBC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely benign (0.0843); Ultra-rare (popmax 0.0632%, mid).

How common is BBC3 p.His103Gln (c.309C>G) in the general population?

BBC3 p.His103Gln (c.309C>G) is ultra-rare (popmax 0.0632%, mid) (gnomAD).

What do computational predictors say about BBC3 p.His103Gln (c.309C>G)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

BBC3 p.His103Gln

c.309C>G · rs764811014 · VCV2347678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0632%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -5.84	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 3.2	GERP 4.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 6,626 bp · p 0.0062 · regional, not allelic
Overall
CADD	17.96	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P138A vs ClinVar H103Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0632% Middle Eastern · 3/4,750 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00914%

Overall 0.00225% 32/1,423,556 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0632%	1,583
Remaining individualsnot grpmax-eligible	0.0055%	18,179
Admixed American	0.003%	33,316
European (non-Finnish)	0.0021%	47,524
African / African-American	0.00151%	66,096
South Asian	0.00147%	68,060

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.His103Gln
Coding: c.309C>G
MANE Select: NM_014417
dbSNP: rs764811014
Type: single nucleotide variant
Location: chr19:47226720 (GRCh38)
Gene constraint: LOEUF 1.293 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 47.60 · 13 PDB
Residue 103: 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-his103gln (accessed [today's date]).

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