Is CAPRIN1 p.Ser498fs (c.1493_1496del) pathogenic?

CAPRIN1 p.Ser498fs (c.14931496del) is classified Pathogenic in CAPRIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-30). Absent from gnomAD; Associated with CAPRIN1-related neurodevelopmental disorders.

What condition is associated with CAPRIN1 p.Ser498fs (c.1493_1496del)?

CAPRIN1 p.Ser498fs (c.1493_1496del) is associated with CAPRIN1-related neurodevelopmental disorders (ClinVar).

How common is CAPRIN1 p.Ser498fs (c.1493_1496del) in the general population?

CAPRIN1 p.Ser498fs (c.1493_1496del) is absent from gnomAD (gnomAD).

CAPRIN1 p.Ser498fs

c.1493_1496del · rs2134131094 · VCV1338774

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CAPRIN1-related neurodevelopmental disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP -0.38, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAPRIN1
Protein: p.Ser498fs
Coding: c.1493_1496del
MANE Select: NM_005898
dbSNP: rs2134131094
Type: Deletion
Location: chr11:34090614 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 6 PDB
Residue 498: 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); the 'disordered' region

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

Disease context

CAPRIN1-related neurodevelopmental disorders

Similar variants

CAPRIN1 p.Ser550fs Likely pathogenic same condition
CAPRIN1 p.Gln419fs Likely pathogenic ★ same condition
CAPRIN1 p.Glu293fs Likely pathogenic ★ same condition
CAPRIN1 p.Ser264Ter Likely pathogenic ★ same condition
CAPRIN1 p.Thr478Ala Uncertain significance ★ ⚠ same condition
CAPRIN1 p.Tyr605Ter Uncertain significance ★ same condition
CAPRIN1 p.Val175Leu Uncertain significance ⚠ same condition
CAPRIN1 p.Ala280fs 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/caprin1-p-ser498fs (accessed [today's date]).

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