SIX5 p.Pro151=
c.453C>G · rs750293326 · VCV2994841
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, amr)
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 -3.7, phastCons 1 |
| Overall | ||
| CADD | 12.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
Admixed American · 3/56,148 alleles
Filtering AF
0.00142%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000693%
Overall
0.000254%
4/1,575,664 alleles · very rare
exomes 3/1,423,466 · genomes 1/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00534% | 18,716 |
| African / African-American | 0.00134% | 74,374 |
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
- SIX5
- Protein
- p.Pro151=
- Coding
- c.453C>G
- MANE Select
- NM_175875
- dbSNP
- rs750293326
- Type
- single nucleotide variant
- Location
- chr19:45768392 (GRCh38)
- Gene constraint
- LOEUF 1.08 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 53.21
Similar variants
- SIX5 p.Ala408Thr Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala411Val Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala584Val Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala626Thr Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala649Ser Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala673Thr Uncertain significance ★★ ⚠ same type
- SIX5 p.Ala722Gly Uncertain significance ★★ ⚠ same type
- SIX5 p.Asp698Glu 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/six5-p-pro151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown