Is PLVAP p.Ser341= (c.1023C>G) pathogenic?

PLVAP p.Ser341= (c.1023C>G) is classified Benign in PLVAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 5.35%, eas) — too common for a highly-penetrant pathogenic allele.

PLVAP p.Ser341=

Q: How common is PLVAP p.Ser341= (c.1023C>G) in the general population?

PLVAP p.Ser341= (c.1023C>G) is common (popmax 5.35%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1023C>G · rs3810208 · VCV2040628

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.35%, eas) — too common for a highly-penetrant pathogenic allele

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 0.98	GERP -3.8, phastCons 0.99
Overall
CADD	7.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.35% East Asian · 2,398/44,858 alleles

Filtering AF 5.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.1%

Overall 0.546% 8,810/1,612,990 alleles · common exomes 6,419/1,460,728 · genomes 2,391/152,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.35%	19
African / African-American	4.15%	24
Admixed American	1.64%	61
South Asian	1.41%	71
Remaining individualsnot grpmax-eligible	0.845%	118
Middle Eastern	0.165%	606
European (non-Finnish)	0.0405%	2,469
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
Finnishnot grpmax-eligible	0.00795%	12,577

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.Ser341=
Coding: c.1023C>G
MANE Select: NM_031310
dbSNP: rs3810208
Type: single nucleotide variant
Location: chr19:17365442 (GRCh38)
Gene constraint: LOEUF 1.015 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39
Residue 341: a UniProt-annotated variant site (in diar10)

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-ser341 (accessed [today's date]).

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