Is WRAP53 p.Lys535= (c.1605A>G) pathogenic?

WRAP53 p.Lys535= (c.1605A>G) is classified Likely benign in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Absent from gnomAD v4.1.

How common is WRAP53 p.Lys535= (c.1605A>G) in the general population?

WRAP53 p.Lys535= (c.1605A>G) is absent from gnomAD v4.1 (gnomAD).

WRAP53 p.Lys535=

c.1605A>G · VCV4754578

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1	GERP -3.6, phastCons 0.99
Overall
CADD	1.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WRAP53
Protein: p.Lys535=
Coding: c.1605A>G
MANE Select: NM_001143992
Type: single nucleotide variant
Location: chr17:7703444 (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 535: the 'disordered' region

Full WRAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WRAP53 p.Lys535Arg Uncertain significance ★★ ⚠ same residue
WRAP53 p.Lys535Glu Uncertain significance ★ ⚠ same residue
WRAP53 c.823-3C>T Uncertain significance ★★ same type
WRAP53 p.Ala118Thr Uncertain significance ★★ ⚠ same type
WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same type
WRAP53 p.Arg298Gln Uncertain significance ★★ ⚠ same type
WRAP53 p.Arg298Gly Uncertain significance ★★ ⚠ same type
WRAP53 p.Arg298Trp Uncertain significance ★★ same type

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-lys535 (accessed [today's date]).

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