Is USB1 p.Ser255= (c.765T>C) pathogenic?

USB1 p.Ser255= (c.765T>C) is classified Likely benign in USB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-12). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Ser255= (c.765T>C)?

USB1 p.Ser255= (c.765T>C) is associated with Inborn genetic diseases (ClinVar).

How common is USB1 p.Ser255= (c.765T>C) in the general population?

USB1 p.Ser255= (c.765T>C) is absent from gnomAD v4.1 (gnomAD).

USB1 p.Ser255=

c.765T>C · rs2544736641 · VCV2188344

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.7
Overall
CADD	6.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: USB1
Protein: p.Ser255=
Coding: c.765T>C
MANE Select: NM_024598
dbSNP: rs2544736641
Type: single nucleotide variant
Location: chr16:58020212 (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 255: 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.Ser255Thr 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
USB1 p.Arg130His 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-ser255 (accessed [today's date]).

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