Is PLIN1 p.Arg231Leu (c.692G>T) pathogenic?

PLIN1 p.Arg231Leu (c.692G>T) is classified Benign in PLIN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1353); Low-frequency (popmax 2.6%, afr); Associated with monogenic diabetes.

What condition is associated with PLIN1 p.Arg231Leu (c.692G>T)?

PLIN1 p.Arg231Leu (c.692G>T) is associated with monogenic diabetes (ClinVar).

How common is PLIN1 p.Arg231Leu (c.692G>T) in the general population?

PLIN1 p.Arg231Leu (c.692G>T) is low-frequency (popmax 2.6%, afr) (gnomAD).

What do computational predictors say about PLIN1 p.Arg231Leu (c.692G>T)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

PLIN1 p.Arg231Leu

c.692G>T · rs114583540 · VCV393438

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.6%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

monogenic diabetes

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.45	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -7.7	GERP -4.8
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.026 · regional, not allelic
Overall
CADD	2.508	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 2.6% African / African-American · 1,953/75,010 alleles

Filtering AF 2.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.47%

Overall 0.142% 2,286/1,613,954 alleles · low-frequency exomes 1,114/1,461,728 · genomes 1,172/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.6%	38
Remaining individualsnot grpmax-eligible	0.221%	453
Admixed American	0.192%	522
Middle Eastern	0.149%	673
South Asian	0.0132%	7,590
European (non-Finnish)	0.005%	19,999

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: PLIN1
Protein: p.Arg231Leu
Coding: c.692G>T
MANE Select: NM_002666
dbSNP: rs114583540
Type: single nucleotide variant
Location: chr15:89669579 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.52

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

Disease context

monogenic diabetes — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLIN1 p.Arg231Ter Uncertain significance ★ same residue
PLIN1 p.Ala271Val Benign ★★ same condition
PLIN1 p.Ser348Leu Benign ★★ same condition
PLIN1 p.Val156Leu Benign ★★ same condition
PLIN1 p.Val272Met Benign/Likely benign ★★ same condition
PLIN1 c.964-1G>A Uncertain significance ★ same condition
PLIN1 p.Ala380Val Conflicting classifications of pathogenicity ★ ⚠ same condition
PLIN1 p.Arg231fs Uncertain significance ★ same residue

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-arg231leu (accessed [today's date]).

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