Is BSCL2 p.Ser255Leu (c.764C>T) pathogenic?

BSCL2 p.Ser255Leu (c.764C>T) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely pathogenic (0.6106); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BSCL2 p.Ser255Leu (c.764C>T)?

BSCL2 p.Ser255Leu (c.764C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BSCL2 p.Ser255Leu (c.764C>T) in the general population?

BSCL2 p.Ser255Leu (c.764C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BSCL2 p.Ser255Leu (c.764C>T)?

AlphaMissense predicts likely pathogenic (score 0.6106) — an in-silico prediction, not a clinical call.

BSCL2 p.Ser255Leu

c.764C>T · rs761806607 · VCV2510841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6106	likely pathogenic
REVEL	0.625	indeterminate
SaProt	LLR -10.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 2,247 bp · p 9.1e-06 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 S191L vs ClinVar S255L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 6.84e-05% 1/1,461,698 alleles · very rare

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: BSCL2
Protein: p.Ser255Leu
Coding: c.764C>T
MANE Select: NM_001122955
dbSNP: rs761806607
Type: single nucleotide variant
Location: chr11:62692664 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BSCL2 p.Ser255= Conflicting classifications of pathogenicity ★ same residue
BSCL2 c.1005+3C>T Uncertain significance ★★ same condition
BSCL2 p.Arg279Cys Uncertain significance ★★ ⚠ same condition
BSCL2 p.Arg341Lys Uncertain significance ★★ same condition
BSCL2 p.Arg89Cys Uncertain significance ★★ ⚠ same condition
BSCL2 p.Asp342Ala Uncertain significance ★★ ⚠ same condition
BSCL2 p.Cys459Ser Uncertain significance ★★ ⚠ same condition
BSCL2 p.Gly358Glu Uncertain significance ★★ ⚠ same condition

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-ser255leu (accessed [today's date]).

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