Is CRIPT p.Phe47fs (c.141del) pathogenic?

CRIPT p.Phe47fs (c.141del) is classified Pathogenic in CRIPT (ClinVar, No assertion criteria, 2 submitters; last evaluated 2014-02-01). Absent from gnomAD v4.1; Associated with Rothmund-Thomson syndrome type 3.

What condition is associated with CRIPT p.Phe47fs (c.141del)?

CRIPT p.Phe47fs (c.141del) is associated with Rothmund-Thomson syndrome type 3, isolated growth hormone deficiency type IA (ClinVar).

How common is CRIPT p.Phe47fs (c.141del) in the general population?

CRIPT p.Phe47fs (c.141del) is absent from gnomAD v4.1 (gnomAD).

How is Rothmund-Thomson syndrome inherited?

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

CRIPT p.Phe47fs

c.141del · rs587779348 · VCV127250

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,790)

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 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -0.46, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,790). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRIPT
Protein: p.Phe47fs
Coding: c.141del
MANE Select: NM_014171
dbSNP: rs587779348
Type: Deletion
Location: chr2:46623765 (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

Also linked: isolated growth hormone deficiency type IA

For Rothmund-Thomson syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CRIPT c.-422_17-582del Pathogenic ★ same condition
CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Cys3fs Pathogenic ★ same condition
CRIPT p.Cys3Tyr Likely 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

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-phe47fs (accessed [today's date]).

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