Is WRAP53 p.Pro11Ser (c.31C>T) pathogenic?

WRAP53 p.Pro11Ser (c.31C>T) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0626); Common (popmax 7.83%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Pro11Ser (c.31C>T)?

WRAP53 p.Pro11Ser (c.31C>T) is associated with dyskeratosis congenita, dyskeratosis congenita, autosomal recessive 3 (ClinVar).

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.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0626) — an in-silico prediction, not a clinical call.

WRAP53 p.Pro11Ser

Q: How common is WRAP53 p.Pro11Ser (c.31C>T) in the general population?

WRAP53 p.Pro11Ser (c.31C>T) is common (popmax 7.83%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.31C>T · rs17880282 · VCV325650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0626 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.83%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.0626	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -6.34	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 0.088	GERP -0.64
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.54 · regional, not allelic
Overall
CADD	10.35	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.83% African / African-American · 5,874/75,028 alleles

Filtering AF 7.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.59%

Overall 0.45% 7,259/1,614,206 alleles · common exomes 3,750/1,461,890 · genomes 3,509/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.83%	13
Admixed American	0.681%	147
Remaining individualsnot grpmax-eligible	0.635%	157
Middle Eastern	0.429%	233
Ashkenazi Jewishnot grpmax-eligible	0.169%	592
European (non-Finnish)	0.0399%	2,505
South Asian	0.0231%	4,337
East Asian	0.02%	4,988
Finnishnot grpmax-eligible	0.00312%	32,020

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_001143992
dbSNP: rs17880282
Type: single nucleotide variant
Location: chr17:7688679 (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 11: a UniProt-annotated variant site (in); the 'disordered' region

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.Pro11Leu Uncertain significance ★ ⚠ same residue
WRAP53 p.Pro11= Likely benign ★ 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-pro11ser (accessed [today's date]).

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