Is PLTP p.Arg133Trp (c.397C>T) pathogenic?

PLTP p.Arg133Trp (c.397C>T) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1429); Ultra-rare (popmax 0.0584%, nfe).

How common is PLTP p.Arg133Trp (c.397C>T) in the general population?

PLTP p.Arg133Trp (c.397C>T) is ultra-rare (popmax 0.0584%, nfe) (gnomAD).

What do computational predictors say about PLTP p.Arg133Trp (c.397C>T)?

AlphaMissense predicts likely benign (score 0.1429) — an in-silico prediction, not a clinical call.

PLTP p.Arg133Trp

c.397C>T · rs138807551 · VCV1432807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1429 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0584%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1429	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -12.05	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 3.4	GERP -0.58, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	25.1	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 0.0584% European (non-Finnish) · 689/1,180,006 alleles

Filtering AF 0.0547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.0454% 733/1,614,006 alleles · ultra-rare exomes 702/1,461,866 · genomes 31/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0584%	1,713
Remaining individualsnot grpmax-eligible	0.0272%	3,676
East Asian	0.0178%	5,611
African / African-American	0.0133%	7,492
Admixed American	0.01%	10,000
South Asian	0.00329%	30,359

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: PLTP
Protein: p.Arg133Trp
Coding: c.397C>T
MANE Select: NM_006227
dbSNP: rs138807551
Type: single nucleotide variant
Location: chr20:45909604 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36

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

Similar variants

PLTP p.Arg133Pro Uncertain significance ★ ⚠ same residue
PLTP p.Arg133Gln Likely benign ★ same residue
PLTP p.Ala155Thr Uncertain significance ★★ ⚠ same type
PLTP p.Ala155Val Uncertain significance ★★ ⚠ same type
PLTP p.Arg177Cys Uncertain significance ★★ ⚠ same type
PLTP p.Arg251Gln Uncertain significance ★★ ⚠ same type
PLTP p.Arg372His Uncertain significance ★★ ⚠ same type
PLTP p.Arg380Gln 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/pltp-p-arg133trp (accessed [today's date]).

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