Is USP13 p.Arg487Trp (c.1459C>T) pathogenic?

USP13 p.Arg487Trp (c.1459C>T) is classified Uncertain significance in USP13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). AlphaMissense: likely benign (0.228); Very rare (popmax 0.00458%, nfe).

How common is USP13 p.Arg487Trp (c.1459C>T) in the general population?

USP13 p.Arg487Trp (c.1459C>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about USP13 p.Arg487Trp (c.1459C>T)?

AlphaMissense predicts likely benign (score 0.228) — an in-silico prediction, not a clinical call.

USP13 p.Arg487Trp

c.1459C>T · rs145234029 · VCV2402046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.228 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.228	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.4, phastCons 0.95
Regional constraint	o/e 0.86	unconstrained · MANE · 131 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.00458% European (non-Finnish) · 54/1,180,048 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.0039% 63/1,614,090 alleles · very rare exomes 58/1,461,884 · genomes 5/152,206 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,853
African / African-American	0.004%	24,972
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,898
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00156%	64,046

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: USP13
Protein: p.Arg487Trp
Coding: c.1459C>T
MANE Select: NM_003940
dbSNP: rs145234029
Type: single nucleotide variant
Location: chr3:179742275 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.80 · 2 PDB
Residue 487: the usp domain

Full USP13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP13 p.Arg487Gln Uncertain significance ★ ⚠ same residue
USP13 c.1921+5C>T Benign/Likely benign ★★ same type
USP13 p.Cys214= Benign ★★ same type
USP13 p.Thr492= Benign ★★ same type
USP13 p.Ala103Val Uncertain significance ★ ⚠ same type
USP13 p.Ala21Thr Uncertain significance ★ ⚠ same type
USP13 p.Ala504Val Uncertain significance ★ ⚠ same type
USP13 p.Ala516Val 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/usp13-p-arg487trp (accessed [today's date]).

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