Is CRIPT c.242-119T>A pathogenic?

CRIPT c.242-119T>A is classified Benign in CRIPT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-18). Common (popmax 27.3%, amr) — too common for a highly-penetrant pathogenic allele.

CRIPT c.242-119T>A

Q: How common is CRIPT c.242-119T>A in the general population?

CRIPT c.242-119T>A is common (popmax 27.3%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs56198684 · VCV1270681

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 27.3%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	acceptor -119	deep intronic (-119 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -2.3
Non-coding constraint	Z 0.89	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	1.485	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.3% Admixed American · 5,805/21,270 alleles

Filtering AF 26.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.5%

Overall 20.9% 89,709/429,278 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	28.1%	4
Admixed Americangrpmax	27.3%	4
European (non-Finnish)	23.8%	4
Amishnot grpmax-eligible	23.3%	4
Middle Eastern	22.4%	4
Remaining individualsnot grpmax-eligible	21.3%	5
South Asian	19.8%	5
Finnishnot grpmax-eligible	19.6%	5
African / African-American	7.34%	14
East Asian	7%	14

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.242-119T>A
MANE Select: NM_014171
dbSNP: rs56198684
Type: single nucleotide variant
Location: chr2:46624044 (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

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-c-242-minus-119t-a (accessed [today's date]).

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