SASH1 p.Ser522=
c.1566C>T · rs768928224 · VCV2656986
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 -0.024 | GERP -0.84, phastCons 0.92 |
| Overall | ||
| CADD | 7.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
Admixed American · 12/60,002 alleles
Filtering AF
0.0115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00898%
Overall
0.00161%
26/1,613,966 alleles · ultra-rare
exomes 24/1,461,758 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.02% | 5,000 |
| South Asian | 0.00878% | 11,385 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.000339% | 295,003 |
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
- SASH1
- Protein
- p.Ser522=
- Coding
- c.1566C>T
- MANE Select
- NM_015278
- dbSNP
- rs768928224
- Type
- single nucleotide variant
- Location
- chr6:148532798 (GRCh38)
- Gene constraint
- LOEUF 0.412 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.90 · 2 PDB
- Residue 522
- the 'disordered' region
Similar variants
- SASH1 p.Ser522Arg Likely pathogenic ★ same residue
- SASH1 p.Arg811Gln Uncertain significance ★★ ⚠ same type
- SASH1 p.Lys134Ile Uncertain significance ★★ ⚠ same type
- SASH1 p.Pro984Leu Uncertain significance ★★ same type
- SASH1 p.Thr460Met Uncertain significance ★★ ⚠ same type
- SASH1 c.337-38G>C Benign ★★ same type
- SASH1 p.Arg1089Gln Benign/Likely benign ★★ same type
- SASH1 p.Arg820Gln Benign/Likely benign ★★ 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/sash1-p-ser522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown