Is BSCL2 p.Phe228= (c.684C>T) pathogenic?

BSCL2 p.Phe228= (c.684C>T) is classified Likely benign in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). Very rare (popmax 0.00119%, nfe); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Phe228= (c.684C>T)?

BSCL2 p.Phe228= (c.684C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Phe228= (c.684C>T) in the general population?

BSCL2 p.Phe228= (c.684C>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

BSCL2 p.Phe228=

c.684C>T · rs745419166 · VCV2889786

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, 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 looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 1.2, phastCons 1
Overall
CADD	15.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,180,034 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00119%	84,288
South Asian	0.0011%	91,082

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.Phe228=
Coding: c.684C>T
dbSNP: rs745419166
Type: single nucleotide variant
Location: chr11:62692744 (GRCh38)

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

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-phe228 (accessed [today's date]).

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