Is PLIN5 p.Ser2Thr (c.4T>A) pathogenic?

PLIN5 p.Ser2Thr (c.4T>A) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0754); Very rare (popmax 0.00271%, nfe).

How common is PLIN5 p.Ser2Thr (c.4T>A) in the general population?

PLIN5 p.Ser2Thr (c.4T>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about PLIN5 p.Ser2Thr (c.4T>A)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

PLIN5 p.Ser2Thr

c.4T>A · rs372134676 · VCV2241050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.46	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 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	19.97	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 0.00271% European (non-Finnish) · 32/1,179,448 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00205% 33/1,612,622 alleles · very rare exomes 28/1,460,436 · genomes 5/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,858
Admixed American	0.00167%	59,858

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.Ser2Thr
Coding: c.4T>A
MANE Select: NM_001013706
dbSNP: rs372134676
Type: single nucleotide variant
Location: chr19:4534071 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 2: the 'essential for lipid droplet targeting' region; the 'interaction with lipe' region; a modified residue (phosphoserine)

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-ser2thr (accessed [today's date]).

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