Is PLVAP p.Arg26Ser (c.76C>A) pathogenic?

PLVAP p.Arg26Ser (c.76C>A) is classified Uncertain significance in PLVAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely pathogenic (0.8719); Ultra-rare (popmax 0.0495%, mid).

How common is PLVAP p.Arg26Ser (c.76C>A) in the general population?

PLVAP p.Arg26Ser (c.76C>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about PLVAP p.Arg26Ser (c.76C>A)?

AlphaMissense predicts likely pathogenic (score 0.8719) — an in-silico prediction, not a clinical call.

PLVAP p.Arg26Ser

c.76C>A · rs761581948 · VCV2078438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8719 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8719	likely pathogenic · top 7% in PLVAP
REVEL	0.134	moderately benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 0.44, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 25 kb · p 0.43 · regional, not allelic
Overall
CADD	24.1	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.000496% 8/1,614,104 alleles · ultra-rare exomes 6/1,461,880 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
European (non-Finnish)	0.000424%	236,002

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.Arg26Ser
Coding: c.76C>A
MANE Select: NM_031310
dbSNP: rs761581948
Type: single nucleotide variant
Location: chr19:17377213 (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-arg26ser (accessed [today's date]).

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