Is CAPRIN2 p.Ile46Thr (c.137T>C) pathogenic?

CAPRIN2 p.Ile46Thr (c.137T>C) is classified Uncertain significance in CAPRIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Very rare (popmax 0.00167%, amr).

How common is CAPRIN2 p.Ile46Thr (c.137T>C) in the general population?

CAPRIN2 p.Ile46Thr (c.137T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

CAPRIN2 p.Ile46Thr

c.137T>C · VCV3827338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.361	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,976 alleles

Overall 0.000124% 2/1,613,434 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,976
European (non-Finnish)	8.47e-05%	1,179,952

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: CAPRIN2
Protein: p.Ile46Thr
Coding: c.137T>C
MANE Select: NM_001385503
Type: single nucleotide variant
Location: chr12:30753384 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB

Full CAPRIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPRIN2 c.1800+5C>T Benign ★★ same type
CAPRIN2 p.Met253Thr Benign ★★ same type
CAPRIN2 p.Ser668= Benign ★★ same type
CAPRIN2 p.Thr763= Benign ★★ same type
CAPRIN2 p.Tyr806= Benign ★★ same type
CAPRIN2 c.-12A>G Uncertain significance ★ same type
CAPRIN2 c.-2A>C Uncertain significance ★ same type
CAPRIN2 c.-30G>A Uncertain significance ★ 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/caprin2-p-ile46thr (accessed [today's date]).

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