CSPP1 p.Val686Ile
c.2056G>A · rs761009916 · VCV3078351
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.194 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.5 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 18.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,346 alleles
Overall
0.000124%
2/1,607,364 alleles · very rare
exomes 1/1,456,294 · genomes 1/151,070 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00135% | 74,346 |
| European (non-Finnish) | 8.49e-05% | 1,177,414 |
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
- CSPP1
- Protein
- p.Val686Ile
- Coding
- c.2056G>A
- MANE Select
- NM_001382391
- dbSNP
- rs761009916
- Type
- single nucleotide variant
- Location
- chr8:67149863 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 57.34
Similar variants
- CSPP1 p.Val686Leu Uncertain significance ★★ same residue
- CSPP1 c.-57C>G Uncertain significance ★★ same condition
- CSPP1 p.Ala38Val Uncertain significance ★★ same condition
- CSPP1 p.Ala523Glu Uncertain significance ★★ same condition
- CSPP1 p.Ala653Val Uncertain significance ★★ same condition
- CSPP1 p.Arg258Lys Uncertain significance ★★ same condition
- CSPP1 p.Arg291Ser Uncertain significance ★★ same condition
- CSPP1 p.Arg314Gln Uncertain significance ★★ 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/cspp1-p-val686ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown