Is CAPRIN2 p.Pro640Leu (c.1919C>T) pathogenic?

CAPRIN2 p.Pro640Leu (c.1919C>T) is classified Uncertain significance in CAPRIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). Very rare (popmax 0.0028%, nfe).

How common is CAPRIN2 p.Pro640Leu (c.1919C>T) in the general population?

CAPRIN2 p.Pro640Leu (c.1919C>T) is very rare (popmax 0.0028%, nfe) (gnomAD).

CAPRIN2 p.Pro640Leu

c.1919C>T · VCV3263262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.075	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.85, phastCons 1
Overall
CADD	17.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% European (non-Finnish) · 33/1,179,840 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00226% 33/1,461,588 alleles · very rare

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.Pro640Leu
Coding: c.1919C>T
MANE Select: NM_001385503
Type: single nucleotide variant
Location: chr12:30719212 (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-pro640leu (accessed [today's date]).

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