Is BSCL2 p.Phe309= (c.927C>T) pathogenic?

BSCL2 p.Phe309= (c.927C>T) is classified Likely benign in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). Very rare (popmax 0.00161%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Phe309= (c.927C>T)?

BSCL2 p.Phe309= (c.927C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Phe309= (c.927C>T) in the general population?

BSCL2 p.Phe309= (c.927C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

BSCL2 p.Phe309=

c.927C>T · rs1346512157 · VCV1640135

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP -2, phastCons 1
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,038 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 19/1,461,890 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.Phe309=
Coding: c.927C>T
MANE Select: NM_001122955
dbSNP: rs1346512157
Type: single nucleotide variant
Location: chr11:62691358 (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.Phe309Ile Uncertain significance ★ ⚠ 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-phe309 (accessed [today's date]).

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