Is PLIN1 p.Pro439fs (c.1308_1309del) pathogenic?

PLIN1 p.Pro439fs (c.13081309del) is classified Pathogenic in PLIN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-21). Very rare (popmax 9.02e-05%, nfe); Associated with PLIN1-related familial partial lipodystrophy.

What condition is associated with PLIN1 p.Pro439fs (c.1308_1309del)?

PLIN1 p.Pro439fs (c.1308_1309del) is associated with PLIN1-related familial partial lipodystrophy (ClinVar).

How common is PLIN1 p.Pro439fs (c.1308_1309del) in the general population?

PLIN1 p.Pro439fs (c.1308_1309del) is very rare (popmax 9.02e-05%, nfe) (gnomAD).

How is PLIN1-related familial partial lipodystrophy inherited?

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

PLIN1 p.Pro439fs

c.1308_1309del · rs2141523598 · VCV1342123

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.02e-05%, nfe)

Conditions

PLIN1-related familial partial lipodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.35	GERP -1.4
Region caveats
Repeat context	tandem	(CGCGCTC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.02e-05% European (non-Finnish) · 1/1,109,232 alleles

Overall 6.84e-05% 1/1,462,792 alleles · very rare exomes 1/1,311,090 · genomes 0/151,702 · 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: PLIN1
Protein: p.Pro439fs
Coding: c.1308_1309del
MANE Select: NM_002666
dbSNP: rs2141523598
Type: Deletion
Location: chr15:89665843 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.52
Residue 439: the 'disordered' region

Full PLIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PLIN1-related familial partial lipodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For PLIN1-related familial partial lipodystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

PLIN1 c.1210-1del Pathogenic ★ same condition
PLIN1 p.Leu68fs Likely pathogenic ★ same condition
PLIN1 p.Val398fs Pathogenic same condition
PLIN1 p.Leu90Pro Uncertain significance ★★ ⚠ same condition
PLIN1 p.Thr345Ala Uncertain significance ★★ ⚠ same condition
PLIN1 c.772-23T>A Benign ★★ same condition
PLIN1 p.Pro194Ala Benign ★★ same condition
PLIN1 p.Pro371= Benign ★★ 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/plin1-p-pro439fs (accessed [today's date]).

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