Is BBC3 p.Glu41Ter (c.121G>T) pathogenic?

BBC3 p.Glu41Ter (c.121G>T) is classified Uncertain significance in BBC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: likely benign (0.2751); Absent from gnomAD v4.1.

How common is BBC3 p.Glu41Ter (c.121G>T) in the general population?

BBC3 p.Glu41Ter (c.121G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBC3 p.Glu41Ter (c.121G>T)?

AlphaMissense predicts likely benign (score 0.2751) — an in-silico prediction, not a clinical call.

BBC3 p.Glu41Ter

c.121G>T · rs2514779643 · VCV2291556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2751 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,224,442)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2751	likely benign
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.20	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 4.6	GERP 2.9, phastCons 1
Overall
CADD	37.0	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. Predicted loss-of-function is descriptive, not an applied PVS1 code.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R75L vs ClinVar E41*) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,224,442). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BBC3
Protein: p.Glu41Ter
Coding: c.121G>T
MANE Select: NM_014417
dbSNP: rs2514779643
Type: single nucleotide variant
Location: chr19:47228311 (GRCh38)
Gene constraint: LOEUF 1.293 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 47.60 · 13 PDB
Residue 41: the 'disordered' region

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

Similar variants

BBC3 p.Glu41Asp Uncertain significance ★ ⚠ same residue
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

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-glu41ter (accessed [today's date]).

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