Is PLIN5 p.Arg348Trp (c.1042C>T) pathogenic?

PLIN5 p.Arg348Trp (c.1042C>T) is classified Uncertain significance in PLIN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1815); Ultra-rare (popmax 0.0176%, mid).

How common is PLIN5 p.Arg348Trp (c.1042C>T) in the general population?

PLIN5 p.Arg348Trp (c.1042C>T) is ultra-rare (popmax 0.0176%, mid) (gnomAD).

What do computational predictors say about PLIN5 p.Arg348Trp (c.1042C>T)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

PLIN5 p.Arg348Trp

c.1042C>T · rs752949459 · VCV2508782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -12.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.63, phastCons 0.85
Regional constraint	o/e 1.08	unconstrained · MANE · 11 kb · p 0.045 · regional, not allelic
Overall
CADD	24.7	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 0.0176% Middle Eastern · 1/5,694 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00529%

Overall 0.0056% 85/1,518,734 alleles · ultra-rare exomes 84/1,366,550 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0176%	5,694
European (non-Finnish)	0.00698%	14,317
Remaining individualsnot grpmax-eligible	0.00339%	29,496
Admixed American	0.00216%	46,260
African / African-American	0.00142%	70,222

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.Arg348Trp
Coding: c.1042C>T
MANE Select: NM_001013706
dbSNP: rs752949459
Type: single nucleotide variant
Location: chr19:4523878 (GRCh38)
Gene constraint: LOEUF 1.525 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.54
Residue 348: the 'interaction with pnpla2 and abhd5' region

Full PLIN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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-arg348trp (accessed [today's date]).

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