INVS p.Arg524=
c.1572A>G · rs187927206 · VCV844289
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, amr)
Conditions
2
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 2.8 | GERP -2.7, phastCons 1 |
| Overall | ||
| CADD | 12.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
Admixed American · 29/60,012 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0299%
Overall
0.00192%
31/1,613,460 alleles · ultra-rare
exomes 29/1,461,312 · genomes 2/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0483% | 2,069 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,248 |
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
- INVS
- Protein
- p.Arg524=
- Coding
- c.1572A>G
- MANE Select
- NM_014425
- dbSNP
- rs187927206
- Type
- single nucleotide variant
- Location
- chr9:100272864 (GRCh38)
- Gene constraint
- LOEUF 0.941 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.76
Similar variants
- INVS c.107-1G>A Likely pathogenic ★★ same condition
- INVS c.1078+1G>A Pathogenic ★★ same condition
- INVS c.1464+1G>T Pathogenic/Likely pathogenic ★★ same condition
- INVS c.2068+2T>C Likely pathogenic ★★ same condition
- INVS c.2069-1G>T Likely pathogenic ★★ same condition
- INVS c.2786+1G>A Pathogenic/Likely pathogenic ★★ same condition
- INVS c.2786+2T>C Pathogenic/Likely pathogenic ★★ same condition
- INVS c.615+1G>A 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/invs-p-arg524 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown