ARVCF p.Pro373=
c.1119C>T · rs1058399 · VCV1290187
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 19.6%, afr) — 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -3.7 |
| Overall | ||
| CADD | 6.534 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
19.6%
African / African-American · 14,624/74,574 alleles
Filtering AF
19.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 19.2%
Overall
1.15%
18,216/1,590,260 alleles · common
exomes 9,570/1,437,982 · genomes 8,646/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 19.6% | 5 |
| Remaining individualsnot grpmax-eligible | 1.54% | 65 |
| Middle Eastern | 1.39% | 72 |
| Admixed American | 1.39% | 72 |
| South Asian | 0.992% | 101 |
| Ashkenazi Jewishnot grpmax-eligible | 0.614% | 163 |
| European (non-Finnish) | 0.0606% | 1,650 |
| East Asian | 0.00687% | 14,561 |
| Finnishnot grpmax-eligible | 0.0033% | 30,302 |
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
- ARVCF
- Protein
- p.Pro373=
- Coding
- c.1119C>T
- MANE Select
- NM_001670
- dbSNP
- rs1058399
- Type
- single nucleotide variant
- Location
- chr22:19980020 (GRCh38)
- Gene constraint
- LOEUF 1.032 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.73
Similar variants
- ARVCF p.Gly172Ser Uncertain significance ★★ ⚠ same type
- ARVCF p.Val958Ile Uncertain significance ★★ ⚠ same type
- ARVCF c.1396+18A>G Benign ★★ same type
- ARVCF c.1396+198C>T Benign ★★ same type
- ARVCF c.1396+40G>A Benign ★★ same type
- ARVCF c.1397-146G>A Benign ★★ same type
- ARVCF c.1397-7C>T Benign ★★ same type
- ARVCF c.1871-172A>C Benign ★★ 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/arvcf-p-pro373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown