Is WRAP53 p.Ser438Phe (c.1313C>T) pathogenic?

WRAP53 p.Ser438Phe (c.1313C>T) is classified Uncertain significance in WRAP53 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1121); Very rare (popmax 0.00186%, nfe); Associated with dyskeratosis congenita.

What condition is associated with WRAP53 p.Ser438Phe (c.1313C>T)?

WRAP53 p.Ser438Phe (c.1313C>T) is associated with dyskeratosis congenita (ClinVar).

How common is WRAP53 p.Ser438Phe (c.1313C>T) in the general population?

WRAP53 p.Ser438Phe (c.1313C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about WRAP53 p.Ser438Phe (c.1313C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

WRAP53 p.Ser438Phe

c.1313C>T · rs1337613715 · VCV1769720

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -1.9, phastCons 0.79
Regional constraint	o/e 0.73	unconstrained · MANE · 932 bp · p 8.6e-05 · regional, not allelic
Overall
CADD	19.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,028 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,974 alleles · very rare exomes 16/1,461,832 · genomes 6/152,142 · joint denominator

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.Ser438Phe
Coding: c.1313C>T
MANE Select: NM_001143992
dbSNP: rs1337613715
Type: single nucleotide variant
Location: chr17:7703037 (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 438: a β-strand

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-ser438phe (accessed [today's date]).

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