SACS p.Pro346=
c.1038G>A · rs771344425 · VCV1093036
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
2
Spastic paraplegia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.023 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.1 | GERP -3.9 |
| Overall | ||
| CADD | 0.978 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00118%
19/1,613,966 alleles · ultra-rare
exomes 18/1,461,884 · genomes 1/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| South Asian | 0.00659% | 15,181 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00134% | 74,866 |
| European (non-Finnish) | 0.000847% | 118,003 |
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
- SACS
- Protein
- p.Pro346=
- Coding
- c.1038G>A
- MANE Select
- NM_014363
- dbSNP
- rs771344425
- Type
- single nucleotide variant
- Location
- chr13:23355574 (GRCh38)
- Gene constraint
- LOEUF 0.644 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- SACS p.Pro346Leu Likely benign ★ same residue
- SACS c.2093+1G>A Likely pathogenic ★★ same condition
- SACS c.604+1G>A Likely pathogenic ★★ same condition
- SACS p.Ala4074Pro Pathogenic ★★ same condition
- SACS p.Arg1575Pro Pathogenic ★★ same condition
- SACS p.Arg1645Gln Likely pathogenic ★★ same condition
- SACS p.Arg1645Ter Pathogenic ★★ same condition
- SACS p.Arg1877Ter 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-pro346 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown