Is PSMB7 p.Pro82Ser (c.244C>T) pathogenic?

PSMB7 p.Pro82Ser (c.244C>T) is classified Uncertain significance in PSMB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1202); Very rare (popmax 0.00997%, sas).

How common is PSMB7 p.Pro82Ser (c.244C>T) in the general population?

PSMB7 p.Pro82Ser (c.244C>T) is very rare (popmax 0.00997%, sas) (gnomAD).

What do computational predictors say about PSMB7 p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.1202) — an in-silico prediction, not a clinical call.

PSMB7 p.Pro82Ser

c.244C>T · VCV3426938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00997%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1202	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -11.43	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 61 kb · p 2.7e-07 · 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 0.00997% South Asian · 9/90,288 alleles

Filtering AF 0.00518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.000751% 12/1,597,652 alleles · very rare exomes 10/1,445,402 · genomes 2/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00997%	10,032
Remaining individualsnot grpmax-eligible	0.00161%	61,964
European (non-Finnish)	0.000171%	583,121

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: PSMB7
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_002799
Type: single nucleotide variant
Location: chr9:124413918 (GRCh38)
Gene constraint: LOEUF 0.427 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 90.42 · 166 PDB

Full PSMB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMB7 p.Ala2Glu Uncertain significance ★ ⚠ same type
PSMB7 p.Ala8Pro Uncertain significance ★ ⚠ same type
PSMB7 p.Ala8Ser Uncertain significance ★ ⚠ same type
PSMB7 p.Glu263Gln Uncertain significance ★ ⚠ same type
PSMB7 p.Leu267Gln Uncertain significance ★ ⚠ same type
PSMB7 p.Tyr7Phe Uncertain significance ★ ⚠ same type
PSMB7 p.Val6Ala 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/psmb7-p-pro82ser (accessed [today's date]).

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