Is PLIN1 p.Ala353Val (c.1058C>T) pathogenic?

PLIN1 p.Ala353Val (c.1058C>T) is classified Uncertain significance in PLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.084); Rare (popmax 0.265%, eas).

How common is PLIN1 p.Ala353Val (c.1058C>T) in the general population?

PLIN1 p.Ala353Val (c.1058C>T) is rare (popmax 0.265%, eas) (gnomAD).

What do computational predictors say about PLIN1 p.Ala353Val (c.1058C>T)?

AlphaMissense predicts likely benign (score 0.084) — an in-silico prediction, not a clinical call.

PLIN1 p.Ala353Val

c.1058C>T · rs551819178 · VCV2364411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.084 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.265%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.084	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.026 · regional, not allelic
Overall
CADD	16.47	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 0.265% East Asian · 119/44,870 alleles

Filtering AF 0.226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0108% 174/1,614,152 alleles · rare exomes 163/1,461,828 · genomes 11/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.265%	377
South Asian	0.0209%	4,794
African / African-American	0.00666%	15,011
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.0022%	45,386
Admixed American	0.00167%	60,030
Finnishnot grpmax-eligible	0.00156%	64,008

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.Ala353Val
Coding: c.1058C>T
MANE Select: NM_002666
dbSNP: rs551819178
Type: single nucleotide variant
Location: chr15:89667087 (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

Similar variants

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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-ala353val (accessed [today's date]).

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