Is VCP p.Arg86= (c.258A>G) pathogenic?

VCP p.Arg86= (c.258A>G) is classified Conflicting classifications of pathogenicity in VCP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2019-07-11). Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

How common is VCP p.Arg86= (c.258A>G) in the general population?

VCP p.Arg86= (c.258A>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

VCP p.Arg86=

Q: What condition is associated with VCP p.Arg86= (c.258A>G)?

VCP p.Arg86= (c.258A>G) is associated with Inborn genetic diseases, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (ClinVar).

c.258A>G · rs1563980979 · VCV594266

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Inborn genetic diseases

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 5	GERP 1.7, phastCons 1
Overall
CADD	15.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,036 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,894 alleles · very rare

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: VCP
Protein: p.Arg86=
Coding: c.258A>G
MANE Select: NM_007126
dbSNP: rs1563980979
Type: single nucleotide variant
Location: chr9:35067935 (GRCh38)
Gene constraint: LOEUF 0.134 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.11 · 144 PDB
Residue 86: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inclusion body myopathy with Paget disease of bone and frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 6

Similar variants

VCP p.Arg86Thr Uncertain significance ★ ⚠ same residue
VCP p.Arg155Cys Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg155Gly Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg155His Pathogenic ★★ ⚠ same condition
VCP p.Arg159Cys Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg159His Pathogenic ★★ same condition
VCP p.Arg191Gln Pathogenic/Likely pathogenic ★★ same condition
VCP p.Arg191Pro Pathogenic/Likely pathogenic ★★ same condition

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/vcp-p-arg86 (accessed [today's date]).

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