Is CRIPTO p.Val22= (c.66C>A) pathogenic?

CRIPTO p.Val22= (c.66C>A) is classified Likely benign in CRIPTO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). Absent from gnomAD v4.1.

How common is CRIPTO p.Val22= (c.66C>A) in the general population?

CRIPTO p.Val22= (c.66C>A) is absent from gnomAD v4.1 (gnomAD).

CRIPTO p.Val22=

c.66C>A · VCV4962076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor loss, 30 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -9.7	GERP -3.1
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRIPTO
Protein: p.Val22=
Coding: c.66C>A
MANE Select: NM_003212
Type: single nucleotide variant
Location: chr3:46579125 (GRCh38)
Structure: AlphaFold pLDDT 67.47
Residue 22: a UniProt-annotated variant site (in)

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

Similar variants

CRIPTO p.Val22Ala Benign ★ same residue
CRIPTO c.339-8A>G Benign ★★ same type
CRIPTO p.Arg111Gly Benign ★★ same type
CRIPTO p.Gly151= Benign/Likely benign ★★ same type
CRIPTO p.Arg111His Uncertain significance ★ ⚠ same type
CRIPTO p.Arg171His Uncertain significance ★ ⚠ same type
CRIPTO p.Arg38Cys Uncertain significance ★ ⚠ same type
CRIPTO p.Arg38His 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/cripto-p-val22 (accessed [today's date]).

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