Is BSCL2 p.Pro149Arg (c.446C>G) pathogenic?

BSCL2 p.Pro149Arg (c.446C>G) is classified Likely pathogenic in BSCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely pathogenic (0.9804); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy.

What condition is associated with BSCL2 p.Pro149Arg (c.446C>G)?

BSCL2 p.Pro149Arg (c.446C>G) is associated with developmental and epileptic encephalopathy (ClinVar).

How common is BSCL2 p.Pro149Arg (c.446C>G) in the general population?

BSCL2 p.Pro149Arg (c.446C>G) is absent from gnomAD v4.1 (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BSCL2 p.Pro149Arg (c.446C>G)?

AlphaMissense predicts likely pathogenic (score 0.9804) — an in-silico prediction, not a clinical call.

BSCL2 p.Pro149Arg

c.446C>G · rs2539174013 · VCV2500763

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9804 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.9804	likely pathogenic ✓ concordant with ClinVar · top 4% in BSCL2
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -16.80	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 13 kb · p 0.65 · regional, not allelic
Overall
CADD	29.3	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 P85R vs ClinVar P149R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BSCL2
Protein: p.Pro149Arg
Coding: c.446C>G
MANE Select: NM_001122955
dbSNP: rs2539174013
Type: single nucleotide variant
Location: chr11:62702508 (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

developmental and epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

BSCL2 p.Pro149Ala Uncertain significance ★ ⚠ same residue
BSCL2 p.Pro149Leu Uncertain significance ★ ⚠ same residue
BSCL2 p.Pro149Thr Uncertain significance ★ ⚠ same residue
BSCL2 c.1006-2A>C Likely pathogenic ★★ same type
BSCL2 c.1006-2A>G Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.486+1G>A Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.631-1G>C Pathogenic/Likely pathogenic ★★ same type
BSCL2 c.766-2A>G Pathogenic ★★ same type

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-pro149arg (accessed [today's date]).

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