Is WRAP53 p.Cys312= (c.936C>T) pathogenic?

WRAP53 p.Cys312= (c.936C>T) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.51%, afr); Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Cys312= (c.936C>T)?

WRAP53 p.Cys312= (c.936C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Cys312= (c.936C>T) in the general population?

WRAP53 p.Cys312= (c.936C>T) is low-frequency (popmax 1.51%, 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.Cys312=

c.936C>T · rs73248508 · VCV325659

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.51%, 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 -8.5	GERP -4
Overall
CADD	1.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.51% African / African-American · 1,136/75,064 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 0.267% 4,305/1,613,614 alleles · low-frequency exomes 3,507/1,461,276 · genomes 798/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.51%	66
Remaining individualsnot grpmax-eligible	0.285%	351
European (non-Finnish)	0.238%	421
Admixed American	0.157%	638
Middle Eastern	0.116%	865
South Asian	0.056%	1,785
Finnishnot grpmax-eligible	0.0486%	2,056
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800

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.Cys312=
Coding: c.936C>T
MANE Select: NM_001143992
dbSNP: rs73248508
Type: single nucleotide variant
Location: chr17:7701770 (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.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-cys312 (accessed [today's date]).

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