Is PLTP p.Pro186Arg (c.557C>G) pathogenic?

PLTP p.Pro186Arg (c.557C>G) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: ambiguous (0.405); Very rare (popmax 8.47e-05%, nfe).

How common is PLTP p.Pro186Arg (c.557C>G) in the general population?

PLTP p.Pro186Arg (c.557C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PLTP p.Pro186Arg (c.557C>G)?

AlphaMissense predicts ambiguous (score 0.405) — an in-silico prediction, not a clinical call.

PLTP p.Pro186Arg

c.557C>G · rs2515469808 · VCV2535291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.405	ambiguous
REVEL	0.515	indeterminate
SaProt	LLR -5.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	27.4	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 8.47e-05% European (non-Finnish) · 1/1,179,942 alleles

Overall 6.2e-05% 1/1,613,724 alleles · very rare exomes 1/1,461,412 · genomes 0/152,312 · joint denominator

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.Pro186Arg
Coding: c.557C>G
MANE Select: NM_006227
dbSNP: rs2515469808
Type: single nucleotide variant
Location: chr20:45907748 (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.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
PLTP p.Arg391Cys Uncertain significance ★★ ⚠ same type
PLTP p.Arg394Pro 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-pro186arg (accessed [today's date]).

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