SP1 p.Ser617=
c.1851G>A · rs374193831 · VCV748746
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00935%, afr)
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 1.2 | GERP -5.5, phastCons 1 |
| Overall | ||
| CADD | 8.884 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,870 alleles
Filtering AF
0.00438%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000992%
16/1,612,936 alleles · very rare
exomes 10/1,460,824 · genomes 6/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00935% | 10,696 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
| South Asian | 0.0011% | 90,958 |
| European (non-Finnish) | 0.000509% | 196,589 |
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
- SP1
- Protein
- p.Ser617=
- Coding
- c.1851G>A
- MANE Select
- NM_138473
- dbSNP
- rs374193831
- Type
- single nucleotide variant
- Location
- chr12:53409368 (GRCh38)
- Gene constraint
- LOEUF 0.169 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 39.98 · 11 PDB
Similar variants
- SP1 p.Ser617Leu Uncertain significance ★ ⚠ same residue
- SP1 p.Leu529= Benign ★★ same type
- SP1 p.Phe785= Likely benign ★★ same type
- SP1 p.Ala13Gly Uncertain significance ★ ⚠ same type
- SP1 p.Ala210Thr Uncertain significance ★ ⚠ same type
- SP1 p.Ala227Gly Uncertain significance ★ ⚠ same type
- SP1 p.Ala275Pro Uncertain significance ★ ⚠ same type
- SP1 p.Ala429Val 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/sp1-p-ser617 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown