Is SQSTM1 p.Pro384= (c.1152A>C) pathogenic?

SQSTM1 p.Pro384= (c.1152A>C) is classified Likely benign in SQSTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Very rare (popmax 0.000339%, nfe); Associated with Paget disease of bone 2, early-onset.

What condition is associated with SQSTM1 p.Pro384= (c.1152A>C)?

SQSTM1 p.Pro384= (c.1152A>C) is associated with Paget disease of bone 2, early-onset, frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (ClinVar).

How common is SQSTM1 p.Pro384= (c.1152A>C) in the general population?

SQSTM1 p.Pro384= (c.1152A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

SQSTM1 p.Pro384=

c.1152A>C · rs944423329 · VCV1664185

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Paget disease of bone 2, early-onset

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 -0.79	GERP -4.1
Overall
CADD	0.408	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,988 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,838 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: SQSTM1
Protein: p.Pro384=
Coding: c.1152A>C
MANE Select: NM_003900
dbSNP: rs944423329
Type: single nucleotide variant
Location: chr5:179833769 (GRCh38)
Gene constraint: LOEUF 1.13 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.81 · 26 PDB
Residue 384: the 'disordered' region; the 'interaction with ntrk1' region

Full SQSTM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Paget disease of bone 2, early-onset — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: frontotemporal dementia and/or amyotrophic lateral sclerosis 1

Similar variants

SQSTM1 p.Pro384Ser Uncertain significance ★★ ⚠ same residue
SQSTM1 p.Pro384Ala Uncertain significance ★ ⚠ same residue
SQSTM1 p.Pro384Leu Uncertain significance ★ ⚠ same residue
SQSTM1 c.301+1G>T Pathogenic/Likely pathogenic ★★ same condition
SQSTM1 p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
SQSTM1 p.Glu389Gln Pathogenic ★★ ⚠ same condition
SQSTM1 p.Met404Val Pathogenic ★★ same condition
SQSTM1 c.1166-5G>A 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/sqstm1-p-pro384 (accessed [today's date]).

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