Is USB1 p.Thr162Pro (c.484A>C) pathogenic?

USB1 p.Thr162Pro (c.484A>C) is classified Uncertain significance in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-30). AlphaMissense: ambiguous (0.3413); Very rare (popmax 0.00333%, amr).

How common is USB1 p.Thr162Pro (c.484A>C) in the general population?

USB1 p.Thr162Pro (c.484A>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about USB1 p.Thr162Pro (c.484A>C)?

AlphaMissense predicts ambiguous (score 0.3413) — an in-silico prediction, not a clinical call.

USB1 p.Thr162Pro

c.484A>C · rs1963565496 · VCV1490430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3413 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3413	ambiguous
REVEL	0.279	benign-leaning
SaProt	LLR -12.59	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.36 · regional, not allelic
Overall
CADD	24.0	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 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00131% 2/152,134 alleles · very rare

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.Thr162Pro
Coding: c.484A>C
MANE Select: NM_024598
dbSNP: rs1963565496
Type: single nucleotide variant
Location: chr16:58014307 (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 162: a β-strand

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

Similar variants

USB1 p.Thr162Ile Uncertain significance ★ ⚠ same residue
USB1 c.266-1G>A Pathogenic ★★ same type
USB1 p.His208Arg Likely pathogenic ★★ same type
USB1 p.Ala106Ser Uncertain significance ★★ ⚠ same type
USB1 p.Ala218Thr Uncertain significance ★★ ⚠ same type
USB1 p.Ala218Val Uncertain significance ★★ ⚠ same type
USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same type
USB1 p.Arg112Trp Uncertain significance ★★ ⚠ same type

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-thr162pro (accessed [today's date]).

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