Is PLTP p.Val164Leu (c.490G>T) pathogenic?

PLTP p.Val164Leu (c.490G>T) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). AlphaMissense: likely benign (0.2882); Very rare (popmax 0.00937%, afr).

How common is PLTP p.Val164Leu (c.490G>T) in the general population?

PLTP p.Val164Leu (c.490G>T) is very rare (popmax 0.00937%, afr) (gnomAD).

What do computational predictors say about PLTP p.Val164Leu (c.490G>T)?

AlphaMissense predicts likely benign (score 0.2882) — an in-silico prediction, not a clinical call.

PLTP p.Val164Leu

c.490G>T · rs1315617401 · VCV1500998

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00937%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2882	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.11	GERP -0.66, phastCons 0.002
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	15.36	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 0.00937% African / African-American · 7/74,668 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.000571% 9/1,575,804 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00937%	10,667
Remaining individualsnot grpmax-eligible	0.00163%	61,244
European (non-Finnish)	8.62e-05%	1,160,626

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.Val164Leu
Coding: c.490G>T
MANE Select: NM_006227
dbSNP: rs1315617401
Type: single nucleotide variant
Location: chr20:45907900 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36
Residue 164: a disulfide bond

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

Similar variants

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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-val164leu (accessed [today's date]).

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