Is USB1 p.Arg130Cys (c.388C>T) pathogenic?

USB1 p.Arg130Cys (c.388C>T) is classified Uncertain significance in USB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-27). AlphaMissense: likely benign (0.1682); Very rare (popmax 0.00768%, sas); Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Arg130Cys (c.388C>T)?

USB1 p.Arg130Cys (c.388C>T) is associated with Inborn genetic diseases (ClinVar).

How common is USB1 p.Arg130Cys (c.388C>T) in the general population?

USB1 p.Arg130Cys (c.388C>T) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about USB1 p.Arg130Cys (c.388C>T)?

AlphaMissense predicts likely benign (score 0.1682) — an in-silico prediction, not a clinical call.

USB1 p.Arg130Cys

c.388C>T · rs769898628 · VCV1493080

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1682	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -13.12	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 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	33.0	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 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00211% 34/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Admixed American	0.00333%	30,000
East Asian	0.00223%	44,874
European (non-Finnish)	0.00169%	59,001
African / African-American	0.00133%	74,912

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.Arg130Cys
Coding: c.388C>T
MANE Select: NM_024598
dbSNP: rs769898628
Type: single nucleotide variant
Location: chr16:58010051 (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 130: 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.Arg130His Uncertain significance ★★ ⚠ same residue
USB1 p.Arg130= Likely benign ★ same residue
USB1 p.Arg130Pro 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

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-arg130cys (accessed [today's date]).

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