SIX1 p.Ser48=
c.144C>T · VCV4921923
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, 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 1.3 | GERP 0.31, phastCons 1 |
| Overall | ||
| CADD | 11.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,179,988 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,613,884 alleles · very rare
exomes 2/1,461,538 · genomes 0/152,346 · joint denominator
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
- SIX1
- Protein
- p.Ser48=
- Coding
- c.144C>T
- MANE Select
- NM_005982
- Type
- single nucleotide variant
- Location
- chr14:60649046 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.87 · 1 PDB
- Residue 48
- an α-helix
Similar variants
- SIX1 p.Ser48Arg Uncertain significance ★ ⚠ same residue
- SIX1 p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
- SIX1 p.Arg110Trp Pathogenic ★★ same type
- SIX1 p.Glu125Lys Pathogenic/Likely pathogenic ★★ same type
- SIX1 p.Tyr129Cys Pathogenic ★★ same type
- SIX1 p.Val106Met Likely pathogenic ★★ same type
- SIX1 p.Ala184Thr Uncertain significance ★★ same type
- SIX1 p.Arg119His 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/six1-p-ser48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown