Is PLTP p.Arg100= (c.300C>T) pathogenic?

PLTP p.Arg100= (c.300C>T) is classified Likely benign in PLTP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). Ultra-rare (popmax 0.0333%, afr).

How common is PLTP p.Arg100= (c.300C>T) in the general population?

PLTP p.Arg100= (c.300C>T) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

PLTP p.Arg100=

c.300C>T · VCV3648195

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -2.9, phastCons 1
Overall
CADD	8.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% African / African-American · 25/75,042 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00279% 45/1,614,130 alleles · ultra-rare exomes 32/1,461,832 · genomes 13/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	3,002
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	8.47e-05%	1,180,004

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.Arg100=
Coding: c.300C>T
MANE Select: NM_006227
Type: single nucleotide variant
Location: chr20:45909971 (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.Arg100His Uncertain significance ★ ⚠ 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
PLTP p.Arg391Cys 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-arg100 (accessed [today's date]).

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