SACS p.Pro547=
c.1641G>A · rs370143541 · VCV1130824
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Conditions
1
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.045 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.9 |
| Overall | ||
| CADD | 0.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,898 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00192%
31/1,614,084 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,980 |
| South Asian | 0.00988% | 10,121 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.00127% | 78,670 |
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
- SACS
- Protein
- p.Pro547=
- Coding
- c.1641G>A
- MANE Select
- NM_014363
- dbSNP
- rs370143541
- Type
- single nucleotide variant
- Location
- chr13:23354971 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- SACS p.Pro547Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SACS p.Pro547Ala Uncertain significance ★ ⚠ same residue
- SACS c.604+1G>A Likely pathogenic ★★ same condition
- SACS p.Arg1877Ter Pathogenic/Likely pathogenic ★★ same condition
- SACS p.Arg1907Ter Pathogenic ★★ same condition
- SACS p.Arg2119Ter Pathogenic ★★ same condition
- SACS p.Arg2425Ter Pathogenic/Likely pathogenic ★★ same condition
- SACS p.Arg2426Ter Pathogenic/Likely pathogenic ★★ 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/sacs-p-pro547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown