Is USB1 p.Pro88Arg (c.263C>G) pathogenic?

USB1 p.Pro88Arg (c.263C>G) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: ambiguous (0.431); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Pro88Arg (c.263C>G)?

USB1 p.Pro88Arg (c.263C>G) is associated with Inborn genetic diseases (ClinVar).

How common is USB1 p.Pro88Arg (c.263C>G) in the general population?

USB1 p.Pro88Arg (c.263C>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about USB1 p.Pro88Arg (c.263C>G)?

AlphaMissense predicts ambiguous (score 0.431) — an in-silico prediction, not a clinical call.

USB1 p.Pro88Arg

c.263C>G · VCV3978188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.431	ambiguous
REVEL	0.492	indeterminate
SaProt	LLR -10.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	28.7	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 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,613,784 alleles · very rare exomes 2/1,461,560 · genomes 0/152,224 · joint denominator

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: USB1
Protein: p.Pro88Arg
Coding: c.263C>G
MANE Select: NM_024598
Type: single nucleotide variant
Location: chr16:58002643 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB
Residue 88: a β-strand

Full USB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USB1 p.Pro88Ser Uncertain significance ★ ⚠ same residue
USB1 p.Pro88= Uncertain significance ★ same residue
USB1 p.Ala106Ser Uncertain significance ★★ ⚠ same condition
USB1 p.Ala218Thr Uncertain significance ★★ ⚠ same condition
USB1 p.Ala218Val Uncertain significance ★★ ⚠ same condition
USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same condition
USB1 p.Arg112Trp Uncertain significance ★★ ⚠ same condition
USB1 p.Arg130Cys Uncertain significance ★★ ⚠ same condition

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/usb1-p-pro88arg (accessed [today's date]).

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