Is USB1 p.His247= (c.741C>T) pathogenic?

USB1 p.His247= (c.741C>T) is classified Likely benign in USB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-28). Very rare (popmax 8.47e-05%, nfe).

How common is USB1 p.His247= (c.741C>T) in the general population?

USB1 p.His247= (c.741C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

USB1 p.His247=

c.741C>T · VCV4765624

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -7.2	GERP -3.7
Overall
CADD	0.091	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 0.000657% 1/152,162 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.His247=
Coding: c.741C>T
MANE Select: NM_024598
Type: single nucleotide variant
Location: chr16:58020188 (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 247: a β-strand

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

Similar variants

USB1 p.His247Pro 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-his247 (accessed [today's date]).

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