Is PLIN3 p.Arg331Trp (c.991C>T) pathogenic?

PLIN3 p.Arg331Trp (c.991C>T) is classified Uncertain significance in PLIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.1083); Ultra-rare (popmax 0.0159%, eas).

How common is PLIN3 p.Arg331Trp (c.991C>T) in the general population?

PLIN3 p.Arg331Trp (c.991C>T) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

What do computational predictors say about PLIN3 p.Arg331Trp (c.991C>T)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

PLIN3 p.Arg331Trp

c.991C>T · VCV3420807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -11.61	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.73, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.8 · regional, not allelic
Overall
CADD	25.1	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 0.0159% East Asian · 7/43,974 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00563%

Overall 0.00273% 42/1,538,282 alleles · ultra-rare exomes 34/1,386,230 · genomes 8/152,052 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,282
African / African-American	0.0137%	7,293
South Asian	0.0112%	8,964
Admixed American	0.00196%	51,082
Remaining individualsnot grpmax-eligible	0.00169%	59,134
Finnishnot grpmax-eligible	0.00164%	61,042
European (non-Finnish)	0.00114%	87,548

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.Arg331Trp
Coding: c.991C>T
MANE Select: NM_005817
Type: single nucleotide variant
Location: chr19:4839506 (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.Arg331Gln Uncertain significance ★ ⚠ same residue
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

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-arg331trp (accessed [today's date]).

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