Is CRIPTO p.Ala144Thr (c.430G>A) pathogenic?

CRIPTO p.Ala144Thr (c.430G>A) is classified Likely benign in CRIPTO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0687); Absent from gnomAD v4.1.

How common is CRIPTO p.Ala144Thr (c.430G>A) in the general population?

CRIPTO p.Ala144Thr (c.430G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRIPTO p.Ala144Thr (c.430G>A)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

CRIPTO p.Ala144Thr

c.430G>A · VCV4656645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -4.51	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 -0.15	GERP -3.1, phastCons 0.02
Regional constraint	o/e 0.91	unconstrained · MANE · 3,277 bp · p 0.14 · regional, not allelic
Overall
CADD	0.126	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

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.Ala144Thr
Coding: c.430G>A
MANE Select: NM_003212
Type: single nucleotide variant
Location: chr3:46580042 (GRCh38)
Structure: AlphaFold pLDDT 67.47
Residue 144: a disulfide bond

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

Similar variants

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
CRIPTO p.Arg60Gln 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-ala144thr (accessed [today's date]).

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