Is PLIN5 p.Arg137Pro (c.410G>C) pathogenic?

PLIN5 p.Arg137Pro (c.410G>C) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.2856); Ultra-rare (popmax 0.0367%, amr).

How common is PLIN5 p.Arg137Pro (c.410G>C) in the general population?

PLIN5 p.Arg137Pro (c.410G>C) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

What do computational predictors say about PLIN5 p.Arg137Pro (c.410G>C)?

AlphaMissense predicts likely benign (score 0.2856) — an in-silico prediction, not a clinical call.

PLIN5 p.Arg137Pro

c.410G>C · rs770558472 · VCV2307942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2856	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP -2.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0367% Admixed American · 22/59,972 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.0018% 29/1,612,970 alleles · ultra-rare exomes 24/1,460,784 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,726
European (non-Finnish)	0.000593%	168,554

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: PLIN5
Protein: p.Arg137Pro
Coding: c.410G>C
MANE Select: NM_001013706
dbSNP: rs770558472
Type: single nucleotide variant
Location: chr19:4529183 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 137: the 'essential for lipid droplet targeting' region

Full PLIN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLIN5 p.Arg137Gln Uncertain significance ★ ⚠ same residue
PLIN5 p.Pro452Leu Uncertain significance ★★ ⚠ same type
PLIN5 p.Ala174Val Uncertain significance ★ ⚠ same type
PLIN5 p.Ala175Pro Uncertain significance ★ ⚠ same type
PLIN5 p.Ala232Thr Uncertain significance ★ ⚠ same type
PLIN5 p.Ala232Val Uncertain significance ★ ⚠ same type
PLIN5 p.Ala310Thr Uncertain significance ★ ⚠ same type
PLIN5 p.Ala341Val 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/plin5-p-arg137pro (accessed [today's date]).

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