Is WRAP53 p.Ala436= (c.1308T>C) pathogenic?

WRAP53 p.Ala436= (c.1308T>C) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Ala436= (c.1308T>C)?

WRAP53 p.Ala436= (c.1308T>C) is associated with dyskeratosis congenita, autosomal recessive 3, dyskeratosis congenita (ClinVar).

How is Dyskeratosis congenita inherited?

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

WRAP53 p.Ala436=

Q: How common is WRAP53 p.Ala436= (c.1308T>C) in the general population?

WRAP53 p.Ala436= (c.1308T>C) is common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1308T>C · rs34016213 · VCV260996

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 14.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.2	GERP -5.1
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.4% African / African-American · 10,789/74,960 alleles

Filtering AF 14.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.1%

Overall 1.22% 19,767/1,614,004 alleles · common exomes 12,943/1,461,840 · genomes 6,824/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.4%	7
Admixed American	1.54%	65
Remaining individualsnot grpmax-eligible	1.46%	69
Middle Eastern	1.4%	71
South Asian	0.873%	115
European (non-Finnish)	0.516%	194
Ashkenazi Jewishnot grpmax-eligible	0.22%	455
Finnishnot grpmax-eligible	0.161%	621
East Asian	0.00669%	14,958

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.Ala436=
Coding: c.1308T>C
MANE Select: NM_001143992
dbSNP: rs34016213
Type: single nucleotide variant
Location: chr17:7703032 (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, 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-ala436 (accessed [today's date]).

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