Is WRAP53 p.Pro240= (c.720A>G) pathogenic?

WRAP53 p.Pro240= (c.720A>G) is classified Conflicting classifications of pathogenicity in WRAP53 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-10-29). Ultra-rare (popmax 0.0412%, nfe); Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Pro240= (c.720A>G)?

WRAP53 p.Pro240= (c.720A>G) is associated with dyskeratosis congenita, autosomal recessive 3, dyskeratosis congenita (ClinVar).

How common is WRAP53 p.Pro240= (c.720A>G) in the general population?

WRAP53 p.Pro240= (c.720A>G) is ultra-rare (popmax 0.0412%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

WRAP53 p.Pro240=

c.720A>G · rs199901527 · VCV744284

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0412%, nfe)

Conditions

dyskeratosis congenita, autosomal recessive 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.36	GERP -4.3, phastCons 0.57
Overall
CADD	8.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0412% European (non-Finnish) · 486/1,178,236 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0369%

Overall 0.0336% 541/1,611,960 alleles · ultra-rare exomes 487/1,459,754 · genomes 54/152,206 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.52%	40
European (non-Finnish)grpmax	0.0412%	2,424
Finnishnot grpmax-eligible	0.0235%	4,262
Remaining individualsnot grpmax-eligible	0.0192%	5,201
African / African-American	0.004%	24,991
Admixed American	0.00333%	29,991

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: WRAP53
Protein: p.Pro240=
Coding: c.720A>G
MANE Select: NM_001143992
dbSNP: rs199901527
Type: single nucleotide variant
Location: chr17:7700818 (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 240: a turn

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

Also linked: dyskeratosis congenita

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.Arg298Gly Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Trp Uncertain significance ★★ same condition
WRAP53 p.Arg301Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg307Trp Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg409Leu Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg483His 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-pro240 (accessed [today's date]).

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