Is PLVAP p.Ser153= (c.459C>T) pathogenic?

PLVAP p.Ser153= (c.459C>T) is classified Likely benign in PLVAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). Very rare (popmax 0.0011%, sas).

How common is PLVAP p.Ser153= (c.459C>T) in the general population?

PLVAP p.Ser153= (c.459C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PLVAP p.Ser153=

c.459C>T · rs1434910770 · VCV2886029

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP -0.48, phastCons 1
Overall
CADD	6.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,064 alleles

Overall 6.2e-05% 1/1,614,114 alleles · very rare exomes 1/1,461,866 · genomes 0/152,248 · 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: PLVAP
Protein: p.Ser153=
Coding: c.459C>T
MANE Select: NM_031310
dbSNP: rs1434910770
Type: single nucleotide variant
Location: chr19:17366106 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39

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

Similar variants

PLVAP p.Arg358Ter Pathogenic ★★ same type
PLVAP p.Ala292Val Uncertain significance ★★ ⚠ same type
PLVAP p.Ala385Thr Uncertain significance ★★ ⚠ same type
PLVAP p.Ala94Thr Uncertain significance ★★ ⚠ same type
PLVAP p.Arg13Trp Uncertain significance ★★ ⚠ same type
PLVAP p.Arg211Cys Uncertain significance ★★ ⚠ same type
PLVAP p.Arg238His Uncertain significance ★★ ⚠ same type
PLVAP p.Arg269Cys 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/plvap-p-ser153 (accessed [today's date]).

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