Is CRIPT p.Tyr50Cys (c.149A>G) pathogenic?

CRIPT p.Tyr50Cys (c.149A>G) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.4459); Ultra-rare (popmax 0.0743%, eas); Associated with Inborn genetic diseases.

What condition is associated with CRIPT p.Tyr50Cys (c.149A>G)?

CRIPT p.Tyr50Cys (c.149A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CRIPT p.Tyr50Cys (c.149A>G) in the general population?

CRIPT p.Tyr50Cys (c.149A>G) is ultra-rare (popmax 0.0743%, eas) (gnomAD).

What do computational predictors say about CRIPT p.Tyr50Cys (c.149A>G)?

AlphaMissense predicts ambiguous (score 0.4459) — an in-silico prediction, not a clinical call.

CRIPT p.Tyr50Cys

c.149A>G · rs577929077 · VCV3077478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4459 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0743%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4459	ambiguous
REVEL	0.595	indeterminate
SaProt	LLR -13.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	28.9	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

Grpmax group 0.0743% East Asian · 33/44,400 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0475%

Overall 0.00319% 51/1,600,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0743%	1,345
South Asian	0.00895%	11,170
African / African-American	0.00806%	12,405
Admixed American	0.00512%	19,523
Remaining individualsnot grpmax-eligible	0.00161%	61,932

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.Tyr50Cys
Coding: c.149A>G
MANE Select: NM_014171
dbSNP: rs577929077
Type: single nucleotide variant
Location: chr2:46623775 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRIPT p.Tyr50Ter Pathogenic ★ same residue
CRIPT p.Ala45Pro Uncertain significance ★★ ⚠ same condition
CRIPT p.Ala84Val Uncertain significance ★★ ⚠ same condition
CRIPT p.Cys86Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Gln74Arg Uncertain significance ★★ ⚠ same condition
CRIPT p.Gly81Val Uncertain significance ★★ ⚠ same condition
CRIPT p.Lys88Arg Uncertain significance ★★ ⚠ same condition
CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition

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-tyr50cys (accessed [today's date]).

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