Is CAPRIN2 p.Met654Val (c.1960A>G) pathogenic?

CAPRIN2 p.Met654Val (c.1960A>G) is classified Uncertain significance in CAPRIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-13). Very rare (popmax 0.000254%, nfe).

How common is CAPRIN2 p.Met654Val (c.1960A>G) in the general population?

CAPRIN2 p.Met654Val (c.1960A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

CAPRIN2 p.Met654Val

c.1960A>G · rs139975710 · VCV2301572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -2.8
Overall
CADD	0.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,960 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,896 alleles · very rare exomes 3/1,461,796 · genomes 1/152,100 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.000254%	393,320

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met654Val
Coding: c.1960A>G
MANE Select: NM_001385503
dbSNP: rs139975710
Type: single nucleotide variant
Location: chr12:30719171 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB
Residue 654: the 'disordered' region

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-met654val (accessed [today's date]).

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