Is CRIPT p.Asp92Gly (c.275A>G) pathogenic?

CRIPT p.Asp92Gly (c.275A>G) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-07). AlphaMissense: ambiguous (0.5466); Very rare (popmax 0.0027%, afr); Associated with CRIPT-related disorder.

What condition is associated with CRIPT p.Asp92Gly (c.275A>G)?

CRIPT p.Asp92Gly (c.275A>G) is associated with CRIPT-related disorder (ClinVar).

How common is CRIPT p.Asp92Gly (c.275A>G) in the general population?

CRIPT p.Asp92Gly (c.275A>G) is very rare (popmax 0.0027%, afr) (gnomAD).

What do computational predictors say about CRIPT p.Asp92Gly (c.275A>G)?

AlphaMissense predicts ambiguous (score 0.5466) — an in-silico prediction, not a clinical call.

CRIPT p.Asp92Gly

c.275A>G · rs748070966 · VCV2632905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Conditions

CRIPT-related disorder

Computational evidence

Protein change
AlphaMissense	0.5466	ambiguous
REVEL	0.544	indeterminate
SaProt	LLR -15.03	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.69, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	24.2	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 0.0027% African / African-American · 2/74,116 alleles

Filtering AF 0.000448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000253% 4/1,583,446 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,058
South Asian	0.00115%	86,726
European (non-Finnish)	8.61e-05%	1,161,512

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.Asp92Gly
Coding: c.275A>G
MANE Select: NM_014171
dbSNP: rs748070966
Type: single nucleotide variant
Location: chr2:46624196 (GRCh38)
Gene constraint: LOEUF 1.852 · pLI 0.19 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.77 · 1 PDB

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

Disease context

CRIPT-related disorder

Similar variants

CRIPT c.83-1G>A Likely pathogenic ★★ same condition
CRIPT p.Lys5Glu Likely benign ⚠ same condition
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-asp92gly (accessed [today's date]).

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