Is CRIPT p.Tyr50Ter (c.150T>A) pathogenic?

CRIPT p.Tyr50Ter (c.150T>A) is classified Pathogenic in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). Very rare (popmax 8.52e-05%, nfe).

How common is CRIPT p.Tyr50Ter (c.150T>A) in the general population?

CRIPT p.Tyr50Ter (c.150T>A) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

CRIPT p.Tyr50Ter

c.150T>A · rs2104174410 · VCV1445347

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.84, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,173,028 alleles

Overall 6.89e-05% 1/1,451,264 alleles · very rare

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: CRIPT
Protein: p.Tyr50Ter
Coding: c.150T>A
MANE Select: NM_014171
dbSNP: rs2104174410
Type: single nucleotide variant
Location: chr2:46623776 (GRCh38)
Gene constraint: LOEUF 1.852 · pLI 0.19 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB
Residue 50: a β-strand

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

Similar variants

CRIPT p.Tyr50Cys Uncertain significance ★ ⚠ same residue
CRIPT c.83-1G>A Likely pathogenic ★★ same type
CRIPT p.Ala45Pro Uncertain significance ★★ ⚠ same type
CRIPT p.Ala84Val Uncertain significance ★★ ⚠ same type
CRIPT p.Cys86Phe Uncertain significance ★★ ⚠ same type
CRIPT p.Gln74Arg Uncertain significance ★★ ⚠ same type
CRIPT p.Gly81Val Uncertain significance ★★ ⚠ same type
CRIPT p.Lys88Arg 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/cript-p-tyr50ter (accessed [today's date]).

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