SPTA1 p.Arg41=
c.121C>A · rs121918640 · VCV1330466
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0252%, nfe)
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 · G>C here scores Δ0.22 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0252%
European (non-Finnish) · 297/1,179,764 alleles
Filtering AF
0.0228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0218%
Overall
0.0208%
335/1,613,616 alleles · ultra-rare
exomes 317/1,461,530 · genomes 18/152,086 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0252% | 3,972 |
| South Asian | 0.0231% | 4,336 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,810 |
| Admixed American | 0.00834% | 11,990 |
| African / African-American | 0.00267% | 37,484 |
| East Asian | 0.00223% | 44,838 |
| Finnishnot grpmax-eligible | 0.00156% | 63,998 |
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.Arg41=
- Coding
- c.121C>A
- MANE Select
- NM_003126
- dbSNP
- rs121918640
- Type
- single nucleotide variant
- Location
- chr1:158685251 (GRCh38)
- Gene constraint
- LOEUF 0.591 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 3 PDB
- Residue 41
- a UniProt-annotated variant site (in el2; tunis); an α-helix
Similar variants
- SPTA1 p.Arg41Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- SPTA1 p.Arg41Trp Pathogenic ⚠ same residue
- 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
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-arg41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown