SIX1 p.Pro38=
c.114C>T · rs752537825 · VCV517563
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, 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 -2.5 | GERP -4.5 |
| Overall | ||
| CADD | 6.648 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,882 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00167%
27/1,613,560 alleles · very rare
exomes 22/1,461,390 · genomes 5/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,882 |
| European (non-Finnish) | 0.00195% | 51,299 |
| Admixed American | 0.00167% | 59,990 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,466 |
| African / African-American | 0.00133% | 74,934 |
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.Pro38=
- Coding
- c.114C>T
- MANE Select
- NM_005982
- dbSNP
- rs752537825
- Type
- single nucleotide variant
- Location
- chr14:60649076 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.87 · 1 PDB
Similar variants
- SIX1 p.Pro38Leu 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-pro38 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown