Is PLIN1 p.Ser217Arg (c.651C>A) pathogenic?

PLIN1 p.Ser217Arg (c.651C>A) is classified Uncertain significance in PLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: ambiguous (0.4644); Absent from gnomAD v4.1.

How common is PLIN1 p.Ser217Arg (c.651C>A) in the general population?

PLIN1 p.Ser217Arg (c.651C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLIN1 p.Ser217Arg (c.651C>A)?

AlphaMissense predicts ambiguous (score 0.4644) — an in-silico prediction, not a clinical call.

PLIN1 p.Ser217Arg

c.651C>A · rs2505540652 · VCV2298136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4644 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4644	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -3.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.38, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.026 · regional, not allelic
Overall
CADD	20.4	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

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: PLIN1
Protein: p.Ser217Arg
Coding: c.651C>A
MANE Select: NM_002666
dbSNP: rs2505540652
Type: single nucleotide variant
Location: chr15:89669620 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.52
Residue 217: the 'disordered' region

Full PLIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLIN1 p.Ala361Glu Uncertain significance ★★ ⚠ same type
PLIN1 p.Arg125Cys Uncertain significance ★★ ⚠ same type
PLIN1 p.Glu151Lys Uncertain significance ★★ ⚠ same type
PLIN1 p.Leu404Phe Uncertain significance ★★ ⚠ same type
PLIN1 p.Leu90Pro Uncertain significance ★★ ⚠ same type
PLIN1 p.Thr345Ala Uncertain significance ★★ ⚠ same type
PLIN1 c.1209+9C>T Benign ★★ same type
PLIN1 c.251-153G>T Benign ★★ 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/plin1-p-ser217arg (accessed [today's date]).

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