Is PLIN1 p.Arg93Ter (c.277C>T) pathogenic?

PLIN1 p.Arg93Ter (c.277C>T) is classified Likely pathogenic in PLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). Very rare (popmax 0.00933%, eas); Associated with PLIN1-related familial partial lipodystrophy.

What condition is associated with PLIN1 p.Arg93Ter (c.277C>T)?

PLIN1 p.Arg93Ter (c.277C>T) is associated with PLIN1-related familial partial lipodystrophy (ClinVar).

How common is PLIN1 p.Arg93Ter (c.277C>T) in the general population?

PLIN1 p.Arg93Ter (c.277C>T) is very rare (popmax 0.00933%, eas) (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.Arg93Ter

c.277C>T · rs150822845 · VCV3065014

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00933%, eas)

Conditions

PLIN1-related familial partial lipodystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -3.3, phastCons 1
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 0.00933% East Asian · 4/42,888 alleles

Filtering AF 0.00746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00697%

Overall 0.00769% 121/1,572,870 alleles · very rare exomes 110/1,420,700 · genomes 11/152,170 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0115%	8,713
East Asiangrpmax	0.00933%	10,722
European (non-Finnish)	0.00889%	11,248
Admixed American	0.00371%	26,922
South Asian	0.00351%	28,483
African / African-American	0.0027%	37,064

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg93Ter
Coding: c.277C>T
MANE Select: NM_002666
dbSNP: rs150822845
Type: single nucleotide variant
Location: chr15:89671538 (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.Arg93Gln Uncertain significance ★ ⚠ 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 c.964-1G>C 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/plin1-p-arg93ter (accessed [today's date]).

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