Is PSMB8 p.Phe80= (c.240C>T) pathogenic?

PSMB8 p.Phe80= (c.240C>T) is classified Conflicting classifications of pathogenicity in PSMB8 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.0039%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with PSMB8 p.Phe80= (c.240C>T)?

PSMB8 p.Phe80= (c.240C>T) is associated with autoinflammatory syndrome, proteosome-associated autoinflammatory syndrome (ClinVar).

How common is PSMB8 p.Phe80= (c.240C>T) in the general population?

PSMB8 p.Phe80= (c.240C>T) is very rare (popmax 0.0039%, nfe) (gnomAD).

PSMB8 p.Phe80=

c.240C>T · rs529946385 · VCV1694137

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Conditions

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 4.5	GERP 1.9, phastCons 1
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% European (non-Finnish) · 46/1,180,048 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00298% 48/1,613,012 alleles · very rare exomes 45/1,460,802 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0039%	25,653
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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.Phe80=
Coding: c.240C>T
MANE Select: NM_148919
dbSNP: rs529946385
Type: single nucleotide variant
Location: chr6:32842997 (GRCh38)
Gene constraint: LOEUF 0.849 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.28 · 22 PDB
Residue 80: a β-strand

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

Disease context

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

Also linked: proteosome-associated autoinflammatory syndrome

Similar variants

PSMB8 p.Phe80Leu Uncertain significance ★★ ⚠ same residue
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.Ala77Thr Uncertain significance ★★ same condition
PSMB8 p.Arg129Cys Uncertain significance ★★ same condition
PSMB8 p.Arg192Gln 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-phe80 (accessed [today's date]).

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