Is BSCL2 p.Pro430Ser (c.1288C>T) pathogenic?

BSCL2 p.Pro430Ser (c.1288C>T) is classified Conflicting classifications of pathogenicity in BSCL2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-12-06). AlphaMissense: likely benign (0.0577); Very rare (popmax 0.00534%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BSCL2 p.Pro430Ser (c.1288C>T)?

BSCL2 p.Pro430Ser (c.1288C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease type 2 (ClinVar).

How common is BSCL2 p.Pro430Ser (c.1288C>T) in the general population?

BSCL2 p.Pro430Ser (c.1288C>T) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about BSCL2 p.Pro430Ser (c.1288C>T)?

AlphaMissense predicts likely benign (score 0.0577) — an in-silico prediction, not a clinical call.

BSCL2 p.Pro430Ser

c.1288C>T · rs377310581 · VCV241723

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0577 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0577	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -3.6, phastCons 0.84
Regional constraint	o/e 1.03	unconstrained · MANE · 2,047 bp · p 0.6 · regional, not allelic
Overall
CADD	6.83	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 P366S vs ClinVar P430S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% European (non-Finnish) · 63/1,180,038 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.00514% 83/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0265%	3,767
European (non-Finnish)grpmax	0.00534%	18,731
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,928
South Asian	0.0011%	91,088

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro430Ser
Coding: c.1288C>T
MANE Select: NM_001122955
dbSNP: rs377310581
Type: single nucleotide variant
Location: chr11:62690468 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease type 2

Similar variants

BSCL2 p.Pro430Thr 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-pro430ser (accessed [today's date]).

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