Is PSMG3 p.Pro5= (c.15G>A) pathogenic?

PSMG3 p.Pro5= (c.15G>A) is classified Likely benign in PSMG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). Very rare (popmax 0.00448%, eas).

How common is PSMG3 p.Pro5= (c.15G>A) in the general population?

PSMG3 p.Pro5= (c.15G>A) is very rare (popmax 0.00448%, eas) (gnomAD).

PSMG3 p.Pro5=

c.15G>A · VCV4146692

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

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 -11	GERP -3.2
Overall
CADD	7.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,598 alleles

Filtering AF 0.000743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000124% 2/1,607,428 alleles · very rare exomes 2/1,455,120 · genomes 0/152,308 · joint denominator

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: PSMG3
Protein: p.Pro5=
Coding: c.15G>A
MANE Select: NM_032302
Type: single nucleotide variant
Location: chr7:1569325 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 93.14 · 4 PDB

Full PSMG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSMG3 p.Pro5Leu Uncertain significance ★ ⚠ same residue
PSMG3 p.Ala98Ser Uncertain significance ★ ⚠ same type
PSMG3 p.Asp3Tyr Uncertain significance ★ ⚠ same type
PSMG3 p.His31Pro Uncertain significance ★ ⚠ same type
PSMG3 p.Pro20Leu Uncertain significance ★ ⚠ same type
PSMG3 p.Ser30Asn Uncertain significance ★ ⚠ same type
PSMG3 p.Thr4Met Uncertain significance ★ ⚠ same type
PSMG3 p.Val19Ile 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/psmg3-p-pro5 (accessed [today's date]).

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