Is WRAP53 p.Met1Val (c.1A>G) pathogenic?

WRAP53 p.Met1Val (c.1A>G) is classified Uncertain significance in WRAP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-01). Ultra-rare (popmax 0.0583%, amr).

How common is WRAP53 p.Met1Val (c.1A>G) in the general population?

WRAP53 p.Met1Val (c.1A>G) is ultra-rare (popmax 0.0583%, amr) (gnomAD).

WRAP53 p.Met1Val

c.1A>G · rs867179605 · VCV1336926

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, amr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.337	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.1	GERP 1.6, phastCons 1
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% Admixed American · 35/60,000 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00273% 44/1,614,052 alleles · ultra-rare exomes 19/1,461,872 · genomes 25/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0583%	1,714
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00133%	74,920
European (non-Finnish)	8.47e-05%	1,180,034

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001143992
dbSNP: rs867179605
Type: single nucleotide variant
Location: chr17:7688649 (GRCh38)

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

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-met1val (accessed [today's date]).

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