Is PLIN5 p.Val199Ala (c.596T>C) pathogenic?

PLIN5 p.Val199Ala (c.596T>C) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely pathogenic (0.6599); Absent from gnomAD v4.1.

How common is PLIN5 p.Val199Ala (c.596T>C) in the general population?

PLIN5 p.Val199Ala (c.596T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLIN5 p.Val199Ala (c.596T>C)?

AlphaMissense predicts likely pathogenic (score 0.6599) — an in-silico prediction, not a clinical call.

PLIN5 p.Val199Ala

c.596T>C · rs2512168061 · VCV2618027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6599 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6599	likely pathogenic · top 9% in PLIN5
REVEL	0.417	indeterminate
SaProt	LLR -10.18	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLIN5
Protein: p.Val199Ala
Coding: c.596T>C
MANE Select: NM_001013706
dbSNP: rs2512168061
Type: single nucleotide variant
Location: chr19:4525757 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 199: the 'interaction with pnpla2 and abhd5' region

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

Similar variants

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
PLIN5 p.Ala356Ser 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-val199ala (accessed [today's date]).

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