Is WRAP53 p.Thr6= (c.18T>A) pathogenic?

WRAP53 p.Thr6= (c.18T>A) is classified Likely benign in WRAP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0283%, amr); Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Thr6= (c.18T>A)?

WRAP53 p.Thr6= (c.18T>A) is associated with dyskeratosis congenita (ClinVar).

How common is WRAP53 p.Thr6= (c.18T>A) in the general population?

WRAP53 p.Thr6= (c.18T>A) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

WRAP53 p.Thr6=

c.18T>A · rs376621917 · VCV723264

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

Conditions

dyskeratosis congenita

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 1.6	GERP -0.82, phastCons 0.086
Overall
CADD	7.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/59,996 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0121% 195/1,613,900 alleles · ultra-rare exomes 174/1,461,712 · genomes 21/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,529
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.0141%	7,108
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00534%	18,731
Finnishnot grpmax-eligible	0.00312%	32,021

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.Thr6=
Coding: c.18T>A
MANE Select: NM_001143992
dbSNP: rs376621917
Type: single nucleotide variant
Location: chr17:7688666 (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 6: 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

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.Arg301Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg409Leu Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg483His Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg52Trp 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-thr6 (accessed [today's date]).

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