Is WRAP53 p.Gln7fs (c.18_19del) pathogenic?

WRAP53 p.Gln7fs (c.1819del) is classified Uncertain significance in WRAP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00508%, nfe); Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Gln7fs (c.18_19del)?

WRAP53 p.Gln7fs (c.18_19del) is associated with dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Gln7fs (c.18_19del) in the general population?

WRAP53 p.Gln7fs (c.18_19del) is very rare (popmax 0.00508%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

WRAP53 p.Gln7fs

c.18_19del · rs764437508 · VCV631791

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00508%, nfe)

Conditions

dyskeratosis congenita, autosomal recessive 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -5.1, phastCons 0.99
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00508% European (non-Finnish) · 60/1,180,022 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00607% 98/1,613,918 alleles · very rare exomes 87/1,461,886 · genomes 11/152,032 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
European (non-Finnish)grpmax	0.00508%	19,667
Remaining individualsnot grpmax-eligible	0.0048%	20,829

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln7fs
Coding: c.18_19del
MANE Select: NM_001143992
dbSNP: rs764437508
Type: Deletion
Location: chr17:7688665 (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 7: the 'disordered' region

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

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.Gly350fs Uncertain significance ★★ same condition
WRAP53 p.Leu373fs Pathogenic ★ same condition
WRAP53 c.956-6del Conflicting classifications of pathogenicity ★ same condition
WRAP53 p.Cys519_Gly520delinsTrp Uncertain significance ★ same condition
WRAP53 p.Gln7Arg Uncertain significance ★ ⚠ same residue
WRAP53 p.Phe419fs Conflicting classifications of pathogenicity ★ same condition
WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Gln 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-gln7fs (accessed [today's date]).

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