Is PLTP p.Gln147Glu (c.439C>G) pathogenic?

PLTP p.Gln147Glu (c.439C>G) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: likely benign (0.0636); Ultra-rare (popmax 0.0173%, afr).

How common is PLTP p.Gln147Glu (c.439C>G) in the general population?

PLTP p.Gln147Glu (c.439C>G) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about PLTP p.Gln147Glu (c.439C>G)?

AlphaMissense predicts likely benign (score 0.0636) — an in-silico prediction, not a clinical call.

PLTP p.Gln147Glu

c.439C>G · rs757314282 · VCV2318436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0636	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP 0.67, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	16.39	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 0.0173% African / African-American · 13/74,936 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000929% 15/1,614,082 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,764
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Gln147Glu
Coding: c.439C>G
MANE Select: NM_006227
dbSNP: rs757314282
Type: single nucleotide variant
Location: chr20:45909562 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36
Residue 147: a disulfide bond

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

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PLTP p.Arg372His Uncertain significance ★★ ⚠ same type
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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/pltp-p-gln147glu (accessed [today's date]).

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