Is WRAP53 p.Asp131fs (c.390del) pathogenic?

WRAP53 p.Asp131fs (c.390del) is classified Uncertain significance in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-17). Very rare (popmax 0.00167%, amr).

How common is WRAP53 p.Asp131fs (c.390del) in the general population?

WRAP53 p.Asp131fs (c.390del) is very rare (popmax 0.00167%, amr) (gnomAD).

WRAP53 p.Asp131fs

c.390del · rs749953879 · VCV2883899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 8.2	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,020 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,190 alleles · very rare exomes 15/1,461,874 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,020
European (non-Finnish)	0.00119%	84,289

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.Asp131fs
Coding: c.390del
MANE Select: NM_001143992
dbSNP: rs749953879
Type: Deletion
Location: chr17:7689037 (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 131: the 'disordered' region

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

Similar variants

WRAP53 p.Gln7fs Uncertain significance ★★ same type
WRAP53 p.Gly350fs Uncertain significance ★★ same type
WRAP53 p.Leu373fs Pathogenic ★ same type
WRAP53 p.Ser456fs Likely pathogenic ★ same type
WRAP53 c.731+3_731+4del Uncertain significance ★ same type
WRAP53 c.823-3del Uncertain significance ★ same type
WRAP53 c.956-6del Conflicting classifications of pathogenicity ★ same type
WRAP53 p.Ala522fs 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-asp131fs (accessed [today's date]).

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