Is BSCL2 p.Phe309Ile (c.925T>A) pathogenic?

BSCL2 p.Phe309Ile (c.925T>A) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely pathogenic (0.5866); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Phe309Ile (c.925T>A)?

BSCL2 p.Phe309Ile (c.925T>A) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Phe309Ile (c.925T>A) in the general population?

BSCL2 p.Phe309Ile (c.925T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSCL2 p.Phe309Ile (c.925T>A)?

AlphaMissense predicts likely pathogenic (score 0.5866) — an in-silico prediction, not a clinical call.

BSCL2 p.Phe309Ile

c.925T>A · rs1201010143 · VCV2730344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5866 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.5866	likely pathogenic
REVEL	0.635	indeterminate
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,047 bp · p 0.6 · regional, not allelic
Overall
CADD	25.4	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 F245I vs ClinVar F309I) — 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.Phe309Ile
Coding: c.925T>A
MANE Select: NM_001122955
dbSNP: rs1201010143
Type: single nucleotide variant
Location: chr11:62691360 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.09 · 1 PDB
Residue 309: the 'disordered' region

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

Disease context

Charcot-Marie-Tooth disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BSCL2 p.Phe309= Likely benign ★ same residue
BSCL2 c.1006-2A>C Likely pathogenic ★★ same condition
BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same condition
BSCL2 p.Ala276Pro Pathogenic ★★ same condition
BSCL2 p.Arg329Ter Pathogenic ★★ same condition
BSCL2 p.Asn152Ser Pathogenic ★★ ⚠ same condition
BSCL2 p.Glu253Ter Pathogenic ★★ same condition
BSCL2 p.Ser154Leu Pathogenic/Likely pathogenic ★★ ⚠ 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-phe309ile (accessed [today's date]).

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