Is BSCL2 p.Pro169Ser (c.505C>T) pathogenic?

BSCL2 p.Pro169Ser (c.505C>T) is classified Uncertain significance in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-11). AlphaMissense: ambiguous (0.3411); Very rare (popmax 0.00133%, afr); Associated with Charcot-Marie-Tooth disease type 2.

What condition is associated with BSCL2 p.Pro169Ser (c.505C>T)?

BSCL2 p.Pro169Ser (c.505C>T) is associated with Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Pro169Ser (c.505C>T) in the general population?

BSCL2 p.Pro169Ser (c.505C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about BSCL2 p.Pro169Ser (c.505C>T)?

AlphaMissense predicts ambiguous (score 0.3411) — an in-silico prediction, not a clinical call.

BSCL2 p.Pro169Ser

c.505C>T · rs878855171 · VCV241724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Charcot-Marie-Tooth disease type 2

Computational evidence

Protein change
AlphaMissense	0.3411	ambiguous
REVEL	0.658	pathogenic-leaning
SaProt	LLR -9.74	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic
Overall
CADD	27.7	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 P105S vs ClinVar P169S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Overall 0.000657% 1/152,128 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.Pro169Ser
Coding: c.505C>T
dbSNP: rs878855171
Type: single nucleotide variant
Location: chr11:62694693 (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-pro169ser (accessed [today's date]).

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