Is PSMB8 p.Phe54= (c.162C>T) pathogenic?

PSMB8 p.Phe54= (c.162C>T) is classified Likely benign in PSMB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). Very rare (popmax 0.00267%, afr); Associated with proteosome-associated autoinflammatory syndrome.

What condition is associated with PSMB8 p.Phe54= (c.162C>T)?

PSMB8 p.Phe54= (c.162C>T) is associated with proteosome-associated autoinflammatory syndrome (ClinVar).

How common is PSMB8 p.Phe54= (c.162C>T) in the general population?

PSMB8 p.Phe54= (c.162C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

PSMB8 p.Phe54=

Q: How is Proteasome-associated autoinflammatory syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.162C>T · rs950306671 · VCV2784453

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

proteosome-associated autoinflammatory syndrome

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 0.66	GERP -3.8, phastCons 0.97
Overall
CADD	5.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,922 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,206 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: PSMB8
Protein: p.Phe54=
Coding: c.162C>T
MANE Select: NM_148919
dbSNP: rs950306671
Type: single nucleotide variant
Location: chr6:32843075 (GRCh38)
Gene constraint: LOEUF 0.849 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28 · 22 PDB

Full PSMB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

proteosome-associated autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Proteasome-associated autoinflammatory syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PSMB8 p.Cys135Ter Pathogenic/Likely pathogenic ★★ same condition
PSMB8 p.Gln161Ter Pathogenic/Likely pathogenic ★★ same condition
PSMB8 p.Thr75Met Pathogenic ★★ same condition
PSMB8 p.Ala224Ser Uncertain significance ★★ ⚠ same condition
PSMB8 p.Arg192Trp Uncertain significance ★★ ⚠ same condition
PSMB8 p.Arg272Trp Uncertain significance ★★ ⚠ same condition
PSMB8 p.Asn157Ser Uncertain significance ★★ ⚠ same condition
PSMB8 p.Gly182Arg 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/psmb8-p-phe54 (accessed [today's date]).

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