Is WRAP53 p.Pro25Ser (c.73C>T) pathogenic?

WRAP53 p.Pro25Ser (c.73C>T) is classified Uncertain significance in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-20). AlphaMissense: likely benign (0.0655); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Pro25Ser (c.73C>T)?

WRAP53 p.Pro25Ser (c.73C>T) is associated with dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Pro25Ser (c.73C>T) in the general population?

WRAP53 p.Pro25Ser (c.73C>T) is absent from gnomAD v4.1 (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about WRAP53 p.Pro25Ser (c.73C>T)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

WRAP53 p.Pro25Ser

c.73C>T · VCV4685783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, autosomal recessive 3

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 0.68, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.54 · regional, not allelic
Overall
CADD	11.41	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: WRAP53
Protein: p.Pro25Ser
Coding: c.73C>T
MANE Select: NM_001143992
Type: single nucleotide variant
Location: chr17:7688721 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.96 · 7 PDB
Residue 25: the 'disordered' region

Full WRAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyskeratosis congenita, autosomal recessive 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Trp Uncertain significance ★★ same condition
WRAP53 p.Arg307Trp Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg483His Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506His Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg52Trp Uncertain significance ★★ ⚠ 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/wrap53-p-pro25ser (accessed [today's date]).

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