Is CRIPT p.Ile82Val (c.244A>G) pathogenic?

CRIPT p.Ile82Val (c.244A>G) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: ambiguous (0.466); Ultra-rare (popmax 0.017%, mid); Associated with Inborn genetic diseases.

What condition is associated with CRIPT p.Ile82Val (c.244A>G)?

CRIPT p.Ile82Val (c.244A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CRIPT p.Ile82Val (c.244A>G) in the general population?

CRIPT p.Ile82Val (c.244A>G) is ultra-rare (popmax 0.017%, mid) (gnomAD).

What do computational predictors say about CRIPT p.Ile82Val (c.244A>G)?

AlphaMissense predicts ambiguous (score 0.466) — an in-silico prediction, not a clinical call.

CRIPT p.Ile82Val

c.244A>G · rs373555322 · VCV2378145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.466 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.466	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -9.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	19.76	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 0.017% Middle Eastern · 1/5,888 alleles

Filtering AF 0.00537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00387%

Overall 0.000832% 13/1,561,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,888
African / African-American	0.0109%	9,183
Remaining individualsnot grpmax-eligible	0.00168%	59,624
European (non-Finnish)	0.000261%	383,057

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.Ile82Val
Coding: c.244A>G
MANE Select: NM_014171
dbSNP: rs373555322
Type: single nucleotide variant
Location: chr2:46624165 (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

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

Similar variants

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
CRIPT p.Ala39Val 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-ile82val (accessed [today's date]).

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