Is WRAP53 p.Pro501Ala (c.1501C>G) pathogenic?

WRAP53 p.Pro501Ala (c.1501C>G) is classified Uncertain significance in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-16). AlphaMissense: likely benign (0.1088); Absent from gnomAD v4.1.

How common is WRAP53 p.Pro501Ala (c.1501C>G) in the general population?

WRAP53 p.Pro501Ala (c.1501C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WRAP53 p.Pro501Ala (c.1501C>G)?

AlphaMissense predicts likely benign (score 0.1088) — an in-silico prediction, not a clinical call.

WRAP53 p.Pro501Ala

c.1501C>G · rs1861948 · VCV1337572

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1088 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1088	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 182 bp · p 0.0044 · regional, not allelic
Overall
CADD	18.16	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

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.Pro501Ala
Coding: c.1501C>G
MANE Select: NM_001143992
dbSNP: rs1861948
Type: single nucleotide variant
Location: chr17:7703340 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.96 · 7 PDB

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

Similar variants

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
WRAP53 p.Arg301Cys Uncertain significance ★★ ⚠ same type
WRAP53 p.Arg307Gln 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-pro501ala (accessed [today's date]).

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