Is WRAP53 p.Arg310Ter (c.928C>T) pathogenic?

WRAP53 p.Arg310Ter (c.928C>T) is classified Uncertain significance in WRAP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). Very rare (popmax 0.00267%, afr).

How common is WRAP53 p.Arg310Ter (c.928C>T) in the general population?

WRAP53 p.Arg310Ter (c.928C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

WRAP53 p.Arg310Ter

c.928C>T · rs761173739 · VCV2421073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 11
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP -1.3, phastCons 1
Overall
CADD	37.0	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 0.00267% African / African-American · 2/74,920 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,613,884 alleles · very rare exomes 6/1,461,680 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,460
European (non-Finnish)	0.000424%	236,008

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.Arg310Ter
Coding: c.928C>T
MANE Select: NM_001143992
dbSNP: rs761173739
Type: single nucleotide variant
Location: chr17:7701762 (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 p.Arg310Gly 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
WRAP53 p.Arg301Cys 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-arg310ter (accessed [today's date]).

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