Is WRAP53 p.Pro136Arg (c.407C>G) pathogenic?

WRAP53 p.Pro136Arg (c.407C>G) is classified Benign/Likely benign in WRAP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.078); Low-frequency (popmax 2.54%, eas); Associated with dyskeratosis congenita, autosomal recessive 3.

What condition is associated with WRAP53 p.Pro136Arg (c.407C>G)?

WRAP53 p.Pro136Arg (c.407C>G) is associated with dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Pro136Arg (c.407C>G) in the general population?

WRAP53 p.Pro136Arg (c.407C>G) is low-frequency (popmax 2.54%, eas) (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.Pro136Arg (c.407C>G)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

WRAP53 p.Pro136Arg

c.407C>G · rs34067256 · VCV261002

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.54%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, autosomal recessive 3

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.04	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 0.5	GERP -1.9
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.54 · regional, not allelic
Overall
CADD	9.371	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.54% East Asian · 1,141/44,878 alleles

Filtering AF 2.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.37%

Overall 0.101% 1,636/1,614,040 alleles · low-frequency exomes 1,349/1,461,822 · genomes 287/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.54%	39
Remaining individualsnot grpmax-eligible	0.483%	207
South Asian	0.108%	929
African / African-American	0.0573%	1,744
Admixed American	0.0383%	2,608
European (non-Finnish)	0.00246%	40,690

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.Pro136Arg
Coding: c.407C>G
MANE Select: NM_001143992
dbSNP: rs34067256
Type: single nucleotide variant
Location: chr17:7689055 (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 136: a UniProt-annotated variant site (in); 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.Pro136= Likely benign ★ same residue
WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Trp Uncertain significance ★★ same condition
WRAP53 p.Arg307Trp Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg483His Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506His 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-pro136arg (accessed [today's date]).

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