Is BSCL2 p.Ser115Phe (c.344C>T) pathogenic?

BSCL2 p.Ser115Phe (c.344C>T) is classified Uncertain significance in BSCL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.9135); Very rare (popmax 0.00333%, amr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Ser115Phe (c.344C>T)?

BSCL2 p.Ser115Phe (c.344C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Ser115Phe (c.344C>T) in the general population?

BSCL2 p.Ser115Phe (c.344C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BSCL2 p.Ser115Phe (c.344C>T)?

AlphaMissense predicts likely pathogenic (score 0.9135) — an in-silico prediction, not a clinical call.

BSCL2 p.Ser115Phe

c.344C>T · rs765023622 · VCV643729

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9135 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.9135	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -12.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic
Overall
CADD	29.8	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 S51F vs ClinVar S115F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,988 alleles · very rare exomes 7/1,461,808 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,998
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000424%	235,998

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.Ser115Phe
Coding: c.344C>T
MANE Select: NM_001122955
dbSNP: rs765023622
Type: single nucleotide variant
Location: chr11:62705361 (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

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

Similar variants

BSCL2 p.Ser115= Likely benign ★★ same residue
BSCL2 p.Ser115Cys 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

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-ser115phe (accessed [today's date]).

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