SALL1 p.Pro1109=
c.3327G>A · rs375357921 · VCV1362643
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Conditions
1
Townes-Brocks syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.1, phastCons 0.32 |
| Overall | ||
| CADD | 10.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,866 alleles
Filtering AF
0.00435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00229%
37/1,614,116 alleles · ultra-rare
exomes 32/1,461,894 · genomes 5/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,973 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| South Asian | 0.00329% | 30,361 |
| European (non-Finnish) | 0.00178% | 56,191 |
| Admixed American | 0.00167% | 60,010 |
| African / African-American | 0.00133% | 75,026 |
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
- SALL1
- Protein
- p.Pro1109=
- Coding
- c.3327G>A
- MANE Select
- NM_002968
- dbSNP
- rs375357921
- Type
- single nucleotide variant
- Location
- chr16:51138895 (GRCh38)
- Gene constraint
- LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.54
- Residue 1109
- the 'disordered' region
Similar variants
- SALL1 p.Pro1109Leu Likely pathogenic ★ ⚠ same residue
- SALL1 p.Arg1054Ter Pathogenic/Likely pathogenic ★★ same condition
- SALL1 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
- SALL1 p.Arg786Ter Pathogenic ★★ same condition
- SALL1 p.Gln272Ter Pathogenic ★★ same condition
- SALL1 p.Gln291Ter Pathogenic/Likely pathogenic ★★ same condition
- SALL1 p.Gln323Ter Pathogenic ★★ same condition
- SALL1 p.Ala369Val Uncertain significance ★★ ⚠ same condition
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/sall1-p-pro1109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown