Is USB1 p.Phe170Ser (c.509T>C) pathogenic?

USB1 p.Phe170Ser (c.509T>C) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-23). AlphaMissense: likely pathogenic (0.979); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Phe170Ser (c.509T>C)?

USB1 p.Phe170Ser (c.509T>C) is associated with Inborn genetic diseases (ClinVar).

How common is USB1 p.Phe170Ser (c.509T>C) in the general population?

USB1 p.Phe170Ser (c.509T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USB1 p.Phe170Ser (c.509T>C)?

AlphaMissense predicts likely pathogenic (score 0.979) — an in-silico prediction, not a clinical call.

USB1 p.Phe170Ser

c.509T>C · VCV4866369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.979	likely pathogenic · top 1% in USB1
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -14.43	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Phe170Ser
Coding: c.509T>C
MANE Select: NM_024598
Type: single nucleotide variant
Location: chr16:58017339 (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 170: 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.Phe170= Likely benign ★ 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-phe170ser (accessed [today's date]).

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