Is BSCL2 p.Val97Ala (c.290T>C) pathogenic?

BSCL2 p.Val97Ala (c.290T>C) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: ambiguous (0.4304); Absent from gnomAD v4.1.

How common is BSCL2 p.Val97Ala (c.290T>C) in the general population?

BSCL2 p.Val97Ala (c.290T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSCL2 p.Val97Ala (c.290T>C)?

AlphaMissense predicts ambiguous (score 0.4304) — an in-silico prediction, not a clinical call.

BSCL2 p.Val97Ala

c.290T>C · VCV3770065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4304 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4304	ambiguous
REVEL	0.383	indeterminate
SaProt	LLR -6.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V33A vs ClinVar V97A) — verify the residue.

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: BSCL2
Protein: p.Val97Ala
Coding: c.290T>C
MANE Select: NM_001122955
Type: single nucleotide variant
Location: chr11:62705415 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB

Full BSCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BSCL2 p.Val97Met Uncertain significance ★★ ⚠ same residue
BSCL2 c.1006-2A>C Likely pathogenic ★★ same type
BSCL2 c.1006-2A>G Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.631-1G>C Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.766-2A>G Pathogenic ★★ same type
BSCL2 p.Ala276Pro Pathogenic ★★ same type
BSCL2 p.Arg202Ter Pathogenic ★★ 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/bscl2-p-val97ala (accessed [today's date]).

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