Is CAPRIN1 p.Leu58Phe (c.172C>T) pathogenic?

CAPRIN1 p.Leu58Phe (c.172C>T) is classified Uncertain significance in CAPRIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely pathogenic (0.6477); Very rare (popmax 0.00133%, afr).

How common is CAPRIN1 p.Leu58Phe (c.172C>T) in the general population?

CAPRIN1 p.Leu58Phe (c.172C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CAPRIN1 p.Leu58Phe (c.172C>T)?

AlphaMissense predicts likely pathogenic (score 0.6477) — an in-silico prediction, not a clinical call.

CAPRIN1 p.Leu58Phe

c.172C>T · VCV4218960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6477	likely pathogenic
REVEL	0.122	moderately benign-leaning
SaProt	LLR -10.26	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.06, phastCons 1
Regional constraint	o/e 1.26	unconstrained · MANE · 173 bp · p 0.016 · regional, not allelic
Overall
CADD	24.6	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

Grpmax group 0.00133% African / African-American · 1/74,988 alleles

Overall 0.000124% 2/1,611,334 alleles · very rare exomes 2/1,459,094 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,988
European (non-Finnish)	8.48e-05%	1,179,188

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: CAPRIN1
Protein: p.Leu58Phe
Coding: c.172C>T
MANE Select: NM_005898
Type: single nucleotide variant
Location: chr11:34052592 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 6 PDB

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

Similar variants

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
CAPRIN1 c.217-5C>G Likely pathogenic ★ same type
CAPRIN1 c.688+5G>A Likely 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-leu58phe (accessed [today's date]).

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