Is PLTP p.Pro204Arg (c.611C>G) pathogenic?

PLTP p.Pro204Arg (c.611C>G) is classified Uncertain significance in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: likely benign (0.3063); Very rare (popmax 0.00667%, afr).

How common is PLTP p.Pro204Arg (c.611C>G) in the general population?

PLTP p.Pro204Arg (c.611C>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about PLTP p.Pro204Arg (c.611C>G)?

AlphaMissense predicts likely benign (score 0.3063) — an in-silico prediction, not a clinical call.

PLTP p.Pro204Arg

c.611C>G · rs143448263 · VCV1940090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3063	likely benign
REVEL	0.519	indeterminate
SaProt	LLR -10.59	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.23	donor gain · deltas
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 13 kb · p 0.099 · regional, not allelic
Overall
CADD	33.0	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 0.00667% African / African-American · 5/74,910 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,613,556 alleles · very rare exomes 3/1,461,392 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,982
Admixed American	0.00167%	59,960

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.Pro204Arg
Coding: c.611C>G
MANE Select: NM_006227
dbSNP: rs143448263
Type: single nucleotide variant
Location: chr20:45907694 (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

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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-pro204arg (accessed [today's date]).

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