SPPL2A p.Ser477=
c.1431A>G · rs747163826 · VCV1663920
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0017%, nfe)
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 -0.26 | GERP -4.3 |
| Overall | ||
| CADD | 9.466 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0017%
European (non-Finnish) · 20/1,179,848 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.0013%
21/1,613,942 alleles · very rare
exomes 21/1,461,590 · genomes 0/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0017% | 58,993 |
| South Asian | 0.0011% | 91,070 |
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
- SPPL2A
- Protein
- p.Ser477=
- Coding
- c.1431A>G
- MANE Select
- NM_032802
- dbSNP
- rs747163826
- Type
- single nucleotide variant
- Location
- chr15:50719997 (GRCh38)
- Gene constraint
- LOEUF 1.074 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28 · 2 PDB
Similar variants
- SPPL2A p.Ala179Val Uncertain significance ★★ ⚠ same type
- SPPL2A p.Ala298Val Uncertain significance ★★ ⚠ same type
- SPPL2A p.Ala480Thr Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg281Cys Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg281His Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg424Thr Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg483His Uncertain significance ★★ same type
- SPPL2A p.Asn66Thr 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/sppl2a-p-ser477 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown