Is PLIN5 p.Pro77Leu (c.230C>T) pathogenic?

PLIN5 p.Pro77Leu (c.230C>T) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely benign (0.2798); Very rare (popmax 0.00368%, nfe).

How common is PLIN5 p.Pro77Leu (c.230C>T) in the general population?

PLIN5 p.Pro77Leu (c.230C>T) is very rare (popmax 0.00368%, nfe) (gnomAD).

What do computational predictors say about PLIN5 p.Pro77Leu (c.230C>T)?

AlphaMissense predicts likely benign (score 0.2798) — an in-silico prediction, not a clinical call.

PLIN5 p.Pro77Leu

c.230C>T · VCV3420873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2798 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00368%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2798	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -11.40	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	27.5	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 0.00368% European (non-Finnish) · 42/1,142,484 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00313% 48/1,532,734 alleles · very rare exomes 46/1,380,490 · genomes 2/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00368%	27,202
Remaining individualsnot grpmax-eligible	0.00336%	29,753
African / African-American	0.00274%	36,447
East Asian	0.00246%	40,710
South Asian	0.00121%	82,876

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.Pro77Leu
Coding: c.230C>T
MANE Select: NM_001013706
Type: single nucleotide variant
Location: chr19:4531653 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 77: the 'essential for lipid droplet targeting' region; the 'interaction with lipe' 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-pro77leu (accessed [today's date]).

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