Is CAPRIN1 p.Pro512Leu (c.1535C>T) pathogenic?

CAPRIN1 p.Pro512Leu (c.1535C>T) is classified Conflicting classifications of pathogenicity in CAPRIN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-03-03). AlphaMissense: likely pathogenic (0.9959); Absent from gnomAD v4.1; Associated with cerebellar ataxia.

What condition is associated with CAPRIN1 p.Pro512Leu (c.1535C>T)?

CAPRIN1 p.Pro512Leu (c.1535C>T) is associated with cerebellar ataxia, neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline (ClinVar).

How common is CAPRIN1 p.Pro512Leu (c.1535C>T) in the general population?

CAPRIN1 p.Pro512Leu (c.1535C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPRIN1 p.Pro512Leu (c.1535C>T)?

AlphaMissense predicts likely pathogenic (score 0.9959) — an in-silico prediction, not a clinical call.

CAPRIN1 p.Pro512Leu

c.1535C>T · rs2496097769 · VCV2664503

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9959 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cerebellar ataxia

Computational evidence

Protein change
AlphaMissense	0.9959	likely pathogenic · top 4% in CAPRIN1
REVEL	0.456	indeterminate
SaProt	LLR -10.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: CAPRIN1
Protein: p.Pro512Leu
Coding: c.1535C>T
MANE Select: NM_005898
dbSNP: rs2496097769
Type: single nucleotide variant
Location: chr11:34090659 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 6 PDB
Residue 512: a UniProt-annotated variant site (in nedlaad; likely pathogenic); a UniProt-annotated variant site (in nedlaad; likely pathogenic; 50% decrease of transcript and protein levels in patient-derived cells compared to controls); a UniProt-annotated variant site (in condcac; likely pathogenic; results in altered dynamics of stress granule formation and resolution; increased protein stability measured by nano-differential scanning fluorimetry; increased protein aggregation; no effect on oligomerization)

Full CAPRIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline

Similar variants

CAPRIN1 c.217-5C>G Likely pathogenic ★ same condition
CAPRIN1 c.1554+2T>C Uncertain significance ★ same condition
CAPRIN1 p.Arg458Ter Pathogenic ★★ same type
CAPRIN1 p.Arg132Cys Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Gln206Arg Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Pro424Leu Uncertain significance ★★ ⚠ same type
CAPRIN1 p.Pro528Thr Uncertain significance ★★ ⚠ same type
CAPRIN1 c.1122+19G>A Benign ★★ 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/caprin1-p-pro512leu (accessed [today's date]).

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