Is WRAP53 p.Phe150= (c.450C>T) pathogenic?

WRAP53 p.Phe150= (c.450C>T) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 28.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Phe150= (c.450C>T)?

WRAP53 p.Phe150= (c.450C>T) 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.Phe150=

Q: How common is WRAP53 p.Phe150= (c.450C>T) in the general population?

WRAP53 p.Phe150= (c.450C>T) is common (popmax 28.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.450C>T · rs2287498 · VCV261003

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 28.6%, eas) — 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 -0.008	GERP -4.6, phastCons 0.77
Overall
CADD	7.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.6% East Asian · 12,847/44,844 alleles

Filtering AF 28.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.1%

Overall 9.79% 157,908/1,613,714 alleles · common exomes 136,744/1,461,822 · genomes 21,164/151,892 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	28.6%	3
African / African-American	24.8%	4
South Asian	21.8%	5
Admixed American	14.7%	7
Remaining individualsnot grpmax-eligible	11.1%	9
Middle Eastern	9.17%	11
Ashkenazi Jewishnot grpmax-eligible	7.85%	13
European (non-Finnish)	7.2%	14
Amishnot grpmax-eligible	5.6%	18
Finnishnot grpmax-eligible	4.68%	21

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.Phe150=
Coding: c.450C>T
MANE Select: NM_001143992
dbSNP: rs2287498
Type: single nucleotide variant
Location: chr17:7689242 (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-phe150 (accessed [today's date]).

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