Is CAPRIN2 p.Ser712Asn (c.2135G>A) pathogenic?

CAPRIN2 p.Ser712Asn (c.2135G>A) is classified Uncertain significance in CAPRIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). Ultra-rare (popmax 0.013%, nfe).

How common is CAPRIN2 p.Ser712Asn (c.2135G>A) in the general population?

CAPRIN2 p.Ser712Asn (c.2135G>A) is ultra-rare (popmax 0.013%, nfe) (gnomAD).

CAPRIN2 p.Ser712Asn

c.2135G>A · rs368121707 · VCV2601957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.095	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 1.5, phastCons 1
Overall
CADD	17.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.013% European (non-Finnish) · 153/1,179,944 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.0103% 167/1,613,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.013%	7,712
African / African-American	0.00401%	24,965

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.Ser712Asn
Coding: c.2135G>A
MANE Select: NM_001385503
dbSNP: rs368121707
Type: single nucleotide variant
Location: chr12:30716594 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.42 · 5 PDB
Residue 712: 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-ser712asn (accessed [today's date]).

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