Is WRAP53 p.Phe293Val (c.877T>G) pathogenic?

WRAP53 p.Phe293Val (c.877T>G) is classified Uncertain significance in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: ambiguous (0.5251); Absent from gnomAD v4.1.

How common is WRAP53 p.Phe293Val (c.877T>G) in the general population?

WRAP53 p.Phe293Val (c.877T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WRAP53 p.Phe293Val (c.877T>G)?

AlphaMissense predicts ambiguous (score 0.5251) — an in-silico prediction, not a clinical call.

WRAP53 p.Phe293Val

c.877T>G · rs2151096446 · VCV1483942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5251 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5251	ambiguous
REVEL	0.353	indeterminate
SaProt	LLR -13.70	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.54 · regional, not allelic
Overall
CADD	27.4	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

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.Phe293Val
Coding: c.877T>G
MANE Select: NM_001143992
dbSNP: rs2151096446
Type: single nucleotide variant
Location: chr17:7701711 (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 293: a β-strand

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-phe293val (accessed [today's date]).

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