Is CAPRIN1 p.Pro683Thr (c.2047C>A) pathogenic?

CAPRIN1 p.Pro683Thr (c.2047C>A) is classified Uncertain significance in CAPRIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-13). AlphaMissense: likely benign (0.1116); Very rare (popmax 0.00549%, sas).

How common is CAPRIN1 p.Pro683Thr (c.2047C>A) in the general population?

CAPRIN1 p.Pro683Thr (c.2047C>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about CAPRIN1 p.Pro683Thr (c.2047C>A)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

CAPRIN1 p.Pro683Thr

c.2047C>A · rs376471525 · VCV1098689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.68, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 23 kb · p 0.059 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,088 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000929% 15/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
European (non-Finnish)	0.000848%	117,993

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.Pro683Thr
Coding: c.2047C>A
MANE Select: NM_005898
dbSNP: rs376471525
Type: single nucleotide variant
Location: chr11:34097743 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 6 PDB
Residue 683: a UniProt-annotated variant site (in nedlaad; likely pathogenic); a UniProt-annotated variant site (in nedlaad; likely pathogenic; 50% decrease of transcript and protein levels in patient-derived cells compared to controls); the 'disordered' region

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

Similar variants

CAPRIN1 p.Pro683Ala Likely benign ★ same residue
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

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-pro683thr (accessed [today's date]).

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