SP7 p.Lys333=
c.999G>A · rs375434848 · VCV1216890
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0999%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.36 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 8.115 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0999%
South Asian · 91/91,092 alleles
Filtering AF
0.0833%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0771%
Overall
0.0423%
682/1,613,852 alleles · ultra-rare
exomes 643/1,461,620 · genomes 39/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0999% | 1,001 |
| Remaining individualsnot grpmax-eligible | 0.0464% | 2,154 |
| European (non-Finnish) | 0.0456% | 2,193 |
| Finnishnot grpmax-eligible | 0.0188% | 5,330 |
| Middle Eastern | 0.0164% | 6,082 |
| African / African-American | 0.00801% | 12,490 |
| Admixed American | 0.00667% | 15,001 |
| East Asian | 0.00223% | 44,900 |
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
- SP7
- Protein
- p.Lys333=
- Coding
- c.999G>A
- MANE Select
- NM_001173467
- dbSNP
- rs375434848
- Type
- single nucleotide variant
- Location
- chr12:53328443 (GRCh38)
- Gene constraint
- LOEUF 0.808 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 52.78
Similar variants
- SP7 p.Lys333Asn Uncertain significance ★ ⚠ same residue
- SP7 p.Ala2Val Uncertain significance ★★ ⚠ same type
- SP7 p.Arg267Cys Uncertain significance ★★ ⚠ same type
- SP7 p.Arg280Leu Uncertain significance ★★ ⚠ same type
- SP7 p.Arg280Trp Uncertain significance ★★ ⚠ same type
- SP7 p.Arg316His Uncertain significance ★★ ⚠ same type
- SP7 p.Arg350Trp Uncertain significance ★★ ⚠ same type
- SP7 p.Arg362His 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/sp7-p-lys333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown