Is CRIPT c.242-19A>T pathogenic?

CRIPT c.242-19A>T is classified Uncertain significance in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-05). Ultra-rare (popmax 0.0345%, mid); Associated with Rothmund-Thomson syndrome type 3.

What condition is associated with CRIPT c.242-19A>T?

CRIPT c.242-19A>T is associated with Rothmund-Thomson syndrome type 3 (ClinVar).

How common is CRIPT c.242-19A>T in the general population?

CRIPT c.242-19A>T is ultra-rare (popmax 0.0345%, mid) (gnomAD).

How is Rothmund-Thomson syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CRIPT c.242-19A>T

rs866376607 · VCV1029251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0345%, mid)

Conditions

Rothmund-Thomson syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	acceptor -19	acceptor splice region (-19, within the last 20 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -2.6
Non-coding constraint	Z 0.89	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0345% Middle Eastern · 2/5,790 alleles

Filtering AF 0.00607% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00251%

Overall 0.000216% 3/1,390,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0345%	2,895
Finnishnot grpmax-eligible	0.00163%	61,422

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.242-19A>T
MANE Select: NM_014171
dbSNP: rs866376607
Type: single nucleotide variant
Location: chr2:46624144 (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

Rothmund-Thomson syndrome type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rothmund-Thomson syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Cys3Tyr Likely pathogenic ★ same condition
CRIPT p.Cys58Ter Likely pathogenic ★ same condition
CRIPT p.Cys76Tyr Pathogenic same condition
CRIPT c.-422_17-582del Pathogenic ★ same condition
CRIPT p.Cys3fs Pathogenic ★ same condition
CRIPT p.Ala45fs Pathogenic same condition
CRIPT p.Phe47fs Pathogenic 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-c-242-minus-19a-t (accessed [today's date]).

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