Is CRIPT p.Arg24Lys (c.71G>A) pathogenic?

CRIPT p.Arg24Lys (c.71G>A) is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-26). AlphaMissense: ambiguous (0.3846); Ultra-rare (popmax 0.0102%, amr).

How common is CRIPT p.Arg24Lys (c.71G>A) in the general population?

CRIPT p.Arg24Lys (c.71G>A) is ultra-rare (popmax 0.0102%, amr) (gnomAD).

What do computational predictors say about CRIPT p.Arg24Lys (c.71G>A)?

AlphaMissense predicts ambiguous (score 0.3846) — an in-silico prediction, not a clinical call.

CRIPT p.Arg24Lys

c.71G>A · rs753774289 · VCV2104700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3846 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3846	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 6,941 bp · p 0.1 · regional, not allelic
Overall
CADD	22.8	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 0.0102% Admixed American · 6/58,762 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.003%

Overall 0.000622% 9/1,447,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0102%	9,794
South Asian	0.00335%	29,855

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.Arg24Lys
Coding: c.71G>A
MANE Select: NM_014171
dbSNP: rs753774289
Type: single nucleotide variant
Location: chr2:46618827 (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 24: a β-strand

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

Similar variants

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
CRIPT p.Ser64Phe 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-arg24lys (accessed [today's date]).

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