Is PLIN3 p.Ser243Leu (c.728C>T) pathogenic?

PLIN3 p.Ser243Leu (c.728C>T) is classified Uncertain significance in PLIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely pathogenic (0.7278); Ultra-rare (popmax 0.0164%, mid).

How common is PLIN3 p.Ser243Leu (c.728C>T) in the general population?

PLIN3 p.Ser243Leu (c.728C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about PLIN3 p.Ser243Leu (c.728C>T)?

AlphaMissense predicts likely pathogenic (score 0.7278) — an in-silico prediction, not a clinical call.

PLIN3 p.Ser243Leu

c.728C>T · rs750348493 · VCV2590219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7278 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7278	likely pathogenic · top 6% in PLIN3
REVEL	0.453	indeterminate
SaProt	LLR -11.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.8 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00297% 48/1,613,620 alleles · ultra-rare exomes 38/1,461,500 · genomes 10/152,120 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.012%	8,324
East Asian	0.00891%	11,220
South Asian	0.00549%	18,207
Finnishnot grpmax-eligible	0.00313%	31,957
European (non-Finnish)	0.0022%	45,382
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: PLIN3
Protein: p.Ser243Leu
Coding: c.728C>T
MANE Select: NM_005817
dbSNP: rs750348493
Type: single nucleotide variant
Location: chr19:4847797 (GRCh38)
Gene constraint: LOEUF 1.213 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.04

Full PLIN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLIN3 p.Lys102= Benign ★★ same type
PLIN3 p.Ala139Thr Uncertain significance ★ ⚠ same type
PLIN3 p.Ala212Val Uncertain significance ★ ⚠ same type
PLIN3 p.Ala215Thr Uncertain significance ★ ⚠ same type
PLIN3 p.Ala371Ser Uncertain significance ★ ⚠ same type
PLIN3 p.Ala397Thr Uncertain significance ★ ⚠ same type
PLIN3 p.Ala397Val Uncertain significance ★ ⚠ same type
PLIN3 p.Ala62Thr Uncertain significance ★ ⚠ same type

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/plin3-p-ser243leu (accessed [today's date]).

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