Is CRIPT p.Cys3fs (c.7_8del) pathogenic?

CRIPT p.Cys3fs (c.78del) is classified Pathogenic in CRIPT (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-09). Very rare (popmax 8.71e-05%, nfe); Associated with Rothmund-Thomson syndrome type 3.

What condition is associated with CRIPT p.Cys3fs (c.7_8del)?

CRIPT p.Cys3fs (c.7_8del) is associated with Rothmund-Thomson syndrome type 3 (ClinVar).

How common is CRIPT p.Cys3fs (c.7_8del) in the general population?

CRIPT p.Cys3fs (c.7_8del) is very rare (popmax 8.71e-05%, nfe) (gnomAD).

How is Rothmund-Thomson syndrome inherited?

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

CRIPT p.Cys3fs

c.7_8del · rs1558716043 · VCV1343340

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.71e-05%, nfe)

Conditions

Rothmund-Thomson syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.71e-05% European (non-Finnish) · 1/1,148,458 alleles

Overall 7.13e-05% 1/1,402,964 alleles · very rare

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.Cys3fs
Coding: c.7_8del
MANE Select: NM_014171
dbSNP: rs1558716043
Type: Microsatellite
Location: chr2:46617286 (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 3: a UniProt-annotated variant site (in rts3)

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.Cys3Tyr Likely pathogenic ★ same residue
CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition
CRIPT c.-422_17-582del Pathogenic ★ same condition
CRIPT p.Cys58Ter Likely pathogenic ★ same condition
CRIPT c.242-19A>T Uncertain significance ★ same condition
CRIPT p.Ala45fs Pathogenic same condition
CRIPT p.Cys76Tyr 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-p-cys3fs (accessed [today's date]).

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