Is PLIN1 p.Arg231Ter (c.691C>T) pathogenic?

PLIN1 p.Arg231Ter (c.691C>T) is classified Uncertain significance in PLIN1 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.004%, afr); Associated with PLIN1-related familial partial lipodystrophy.

What condition is associated with PLIN1 p.Arg231Ter (c.691C>T)?

PLIN1 p.Arg231Ter (c.691C>T) is associated with PLIN1-related familial partial lipodystrophy (ClinVar).

How common is PLIN1 p.Arg231Ter (c.691C>T) in the general population?

PLIN1 p.Arg231Ter (c.691C>T) is very rare (popmax 0.004%, afr) (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.Arg231Ter

c.691C>T · rs974117029 · VCV1339162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

PLIN1-related familial partial lipodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 9
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.1	GERP 0.36, phastCons 0.87
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,920 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,613,858 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000254%	393,312

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.Arg231Ter
Coding: c.691C>T
MANE Select: NM_002666
dbSNP: rs974117029
Type: single nucleotide variant
Location: chr15:89669580 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.52

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 p.Arg231Leu Benign ★★ same residue
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
PLIN1 p.Val373= Benign ★★ same condition
PLIN1 p.Arg93Ter Likely pathogenic ★ 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-arg231ter (accessed [today's date]).

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