Is WRAP53 p.Glu494= (c.1482A>G) pathogenic?

WRAP53 p.Glu494= (c.1482A>G) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.73%, afr); Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Glu494= (c.1482A>G)?

WRAP53 p.Glu494= (c.1482A>G) is associated with dyskeratosis congenita (ClinVar).

How common is WRAP53 p.Glu494= (c.1482A>G) in the general population?

WRAP53 p.Glu494= (c.1482A>G) is low-frequency (popmax 1.73%, 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.Glu494=

c.1482A>G · rs140360074 · VCV260998

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.73%, afr)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -0.54, phastCons 0.7
Overall
CADD	2.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.73% African / African-American · 1,297/74,954 alleles

Filtering AF 1.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.62%

Overall 0.0946% 1,526/1,613,888 alleles · low-frequency exomes 775/1,461,792 · genomes 751/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.73%	58
Admixed American	0.2%	500
Remaining individualsnot grpmax-eligible	0.146%	687
Middle Eastern	0.0825%	1,212
South Asian	0.00659%	15,178
European (non-Finnish)	0.000593%	168,571

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.Glu494=
Coding: c.1482A>G
MANE Select: NM_001143992
dbSNP: rs140360074
Type: single nucleotide variant
Location: chr17:7703321 (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 494: a UniProt-annotated variant site (in)

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

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.Glu494Lys Uncertain significance ★★ ⚠ same residue
WRAP53 p.Glu494Gly 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.Arg301Cys 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-glu494 (accessed [today's date]).

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