Is WRAP53 p.Arg269= (c.807C>T) pathogenic?

WRAP53 p.Arg269= (c.807C>T) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.23%, afr); Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Arg269= (c.807C>T)?

WRAP53 p.Arg269= (c.807C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Arg269= (c.807C>T) in the general population?

WRAP53 p.Arg269= (c.807C>T) is low-frequency (popmax 1.23%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

WRAP53 p.Arg269=

c.807C>T · rs35307405 · VCV619289

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.23%, afr)

Conditions

dyskeratosis congenita

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 -11	GERP -4.1
Overall
CADD	1.547	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.23% African / African-American · 923/75,058 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.0659% 1,063/1,614,244 alleles · low-frequency exomes 509/1,461,880 · genomes 554/152,364 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.23%	81
Middle Eastern	0.132%	758
Admixed American	0.102%	984
Remaining individualsnot grpmax-eligible	0.0768%	1,302
East Asian	0.00446%	22,441
South Asian	0.00439%	22,773
European (non-Finnish)	0.00144%	69,415

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.Arg269=
Coding: c.807C>T
MANE Select: NM_001143992
dbSNP: rs35307405
Type: single nucleotide variant
Location: chr17:7701534 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.96 · 7 PDB

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

Disease context

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

Also linked: dyskeratosis congenita, autosomal recessive 3

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.Arg269Gly Uncertain significance ★ ⚠ same residue
WRAP53 p.Arg269His Uncertain significance ★ ⚠ same residue
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

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-arg269 (accessed [today's date]).

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