Is PLIN3 p.Pro352Ser (c.1054C>T) pathogenic?

PLIN3 p.Pro352Ser (c.1054C>T) is classified Uncertain significance in PLIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.3893); Ultra-rare (popmax 0.0157%, eas).

How common is PLIN3 p.Pro352Ser (c.1054C>T) in the general population?

PLIN3 p.Pro352Ser (c.1054C>T) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

What do computational predictors say about PLIN3 p.Pro352Ser (c.1054C>T)?

AlphaMissense predicts ambiguous (score 0.3893) — an in-silico prediction, not a clinical call.

PLIN3 p.Pro352Ser

c.1054C>T · rs369436682 · VCV2466733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3893 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Computational evidence

Protein change
AlphaMissense	0.3893	ambiguous
REVEL	0.523	indeterminate
SaProt	LLR -12.52	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.8 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% East Asian · 7/44,530 alleles

Filtering AF 0.00731% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00518%

Overall 0.001% 16/1,597,144 alleles · ultra-rare exomes 12/1,444,898 · genomes 4/152,246 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,361
Remaining individualsnot grpmax-eligible	0.0146%	6,856

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.Pro352Ser
Coding: c.1054C>T
MANE Select: NM_005817
dbSNP: rs369436682
Type: single nucleotide variant
Location: chr19:4839443 (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-pro352ser (accessed [today's date]).

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