Is PLIN3 p.Arg247Trp (c.739C>T) pathogenic?

PLIN3 p.Arg247Trp (c.739C>T) is classified Uncertain significance in PLIN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.2489); Very rare (popmax 0.00446%, eas).

How common is PLIN3 p.Arg247Trp (c.739C>T) in the general population?

PLIN3 p.Arg247Trp (c.739C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about PLIN3 p.Arg247Trp (c.739C>T)?

AlphaMissense predicts likely benign (score 0.2489) — an in-silico prediction, not a clinical call.

PLIN3 p.Arg247Trp

c.739C>T · VCV4139694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2489	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -13.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP -0.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 22 kb · p 0.8 · regional, not allelic
Overall
CADD	26.3	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 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00155% 25/1,613,248 alleles · very rare exomes 22/1,461,114 · genomes 3/152,134 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
African / African-American	0.00267%	37,463
European (non-Finnish)	0.00161%	62,093
Remaining individualsnot grpmax-eligible	0.0016%	62,448
South Asian	0.0011%	91,022

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.Arg247Trp
Coding: c.739C>T
MANE Select: NM_005817
Type: single nucleotide variant
Location: chr19:4847786 (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.Arg247Gln 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-arg247trp (accessed [today's date]).

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