Is PLIN1 p.Val373= (c.1119C>T) pathogenic?

PLIN1 p.Val373= (c.1119C>T) is classified Benign in PLIN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-04-26). Common (popmax 40.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with PLIN1-related familial partial lipodystrophy.

What condition is associated with PLIN1 p.Val373= (c.1119C>T)?

PLIN1 p.Val373= (c.1119C>T) is associated with PLIN1-related familial partial lipodystrophy (ClinVar).

How is PLIN1-related familial partial lipodystrophy inherited?

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

PLIN1 p.Val373=

Q: How common is PLIN1 p.Val373= (c.1119C>T) in the general population?

PLIN1 p.Val373= (c.1119C>T) is common (popmax 40.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1119C>T · rs2304796 · VCV129971

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 40.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

PLIN1-related familial partial lipodystrophy

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 2.7	GERP -2.2, phastCons 0.14
Overall
CADD	6.839	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.4% South Asian · 36,748/91,062 alleles

Filtering AF 40% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.9%

Overall 30% 483,990/1,613,584 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	40.4%	2
Amishnot grpmax-eligible	37%	3
Ashkenazi Jewishnot grpmax-eligible	36.1%	3
Middle Eastern	32.4%	3
European (non-Finnish)	30.9%	3
Remaining individualsnot grpmax-eligible	30.5%	3
East Asian	28.2%	4
Finnishnot grpmax-eligible	20.8%	5
Admixed American	19.8%	5
African / African-American	16.9%	6

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.Val373=
Coding: c.1119C>T
MANE Select: NM_002666
dbSNP: rs2304796
Type: single nucleotide variant
Location: chr15:89667026 (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.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.Arg93Ter Likely pathogenic ★ same condition
PLIN1 c.964-1G>C Uncertain significance ★ same condition
PLIN1 p.Arg168Ter 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-val373 (accessed [today's date]).

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