SPTA1 p.Phe2276=
c.6828T>C · VCV4916683
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0737%, eas)
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 1.8 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 5.905 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0737%
East Asian · 33/44,778 alleles
Filtering AF
0.0539%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0471%
Overall
0.00232%
37/1,597,898 alleles · ultra-rare
exomes 31/1,445,652 · genomes 6/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0737% | 1,357 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,985 |
| South Asian | 0.0011% | 90,616 |
| European (non-Finnish) | 8.58e-05% | 1,165,556 |
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
- SPTA1
- Protein
- p.Phe2276=
- Coding
- c.6828T>C
- MANE Select
- NM_003126
- Type
- single nucleotide variant
- Location
- chr1:158614267 (GRCh38)
- Gene constraint
- LOEUF 0.591 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 3 PDB
- Residue 2276
- the ef-hand 1 domain
Similar variants
- SPTA1 c.1350+1G>C Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.1833+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.24+1G>A Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.2464+1G>A Likely pathogenic ★★ same type
- SPTA1 c.2806-13T>G Pathogenic/Likely pathogenic ★★ same type
- SPTA1 c.2898+2T>C Likely pathogenic ★★ same type
- SPTA1 c.390+1G>A Likely pathogenic ★★ same type
- SPTA1 c.4339-99C>T Pathogenic/Likely pathogenic ★★ 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/spta1-p-phe2276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown