Is CRIPT p.Cys58Ter (c.174T>A) pathogenic?

CRIPT p.Cys58Ter (c.174T>A) is classified Likely pathogenic in CRIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-19). Absent from gnomAD v4.1; Associated with Rothmund-Thomson syndrome type 3.

What condition is associated with CRIPT p.Cys58Ter (c.174T>A)?

CRIPT p.Cys58Ter (c.174T>A) is associated with Rothmund-Thomson syndrome type 3 (ClinVar).

How common is CRIPT p.Cys58Ter (c.174T>A) in the general population?

CRIPT p.Cys58Ter (c.174T>A) 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.Cys58Ter

c.174T>A · VCV4850400

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Rothmund-Thomson syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.31, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRIPT
Protein: p.Cys58Ter
Coding: c.174T>A
MANE Select: NM_014171
Type: single nucleotide variant
Location: chr2:46623800 (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.Cys58= Likely benign ★ same residue
CRIPT p.Ser64Phe Uncertain significance ★★ ⚠ same condition
CRIPT p.Cys3Tyr Likely pathogenic ★ same condition
CRIPT c.242-19A>T Uncertain significance ★ 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

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-cys58ter (accessed [today's date]).

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