Is USB1 p.Ser147Pro (c.439T>C) pathogenic?

USB1 p.Ser147Pro (c.439T>C) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely benign (0.0792); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with USB1 p.Ser147Pro (c.439T>C)?

USB1 p.Ser147Pro (c.439T>C) is associated with Inborn genetic diseases (ClinVar).

How common is USB1 p.Ser147Pro (c.439T>C) in the general population?

USB1 p.Ser147Pro (c.439T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about USB1 p.Ser147Pro (c.439T>C)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

USB1 p.Ser147Pro

c.439T>C · VCV4634194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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.Ser147Pro
Coding: c.439T>C
MANE Select: NM_024598
Type: single nucleotide variant
Location: chr16:58010102 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB

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.Ser147Ala Uncertain significance ★ ⚠ same residue
USB1 p.Ser147= 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

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-ser147pro (accessed [today's date]).

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