SAG p.Val351=
c.1053C>T · rs377460398 · VCV1108662
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0136%, 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 4.4 | GERP -2.8, phastCons 1 |
| Overall | ||
| CADD | 14.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0136%
Admixed American · 8/59,020 alleles
Filtering AF
0.00671%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00489%
Overall
0.00492%
79/1,606,546 alleles · ultra-rare
exomes 69/1,454,346 · genomes 10/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0136% | 7,378 |
| Remaining individualsnot grpmax-eligible | 0.00643% | 15,559 |
| European (non-Finnish) | 0.00561% | 17,818 |
| African / African-American | 0.00133% | 74,934 |
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
- SAG
- Protein
- p.Val351=
- Coding
- c.1053C>T
- MANE Select
- NM_000541
- dbSNP
- rs377460398
- Type
- single nucleotide variant
- Location
- chr2:233342277 (GRCh38)
- Structure
- AlphaFold pLDDT 83.02 · 7 PDB
Similar variants
- SAG p.Val351fs Likely pathogenic ★ same residue
- SAG c.1023-2A>G Likely pathogenic ★★ same type
- SAG c.1103-2A>C Pathogenic/Likely pathogenic ★★ same type
- SAG c.136+2T>C Likely pathogenic ★★ same type
- SAG c.136+2T>G Pathogenic/Likely pathogenic ★★ same type
- SAG c.181+1G>A Likely pathogenic ★★ same type
- SAG c.182-2A>G Pathogenic/Likely pathogenic ★★ same type
- SAG c.376-2A>G Pathogenic/Likely pathogenic ★★ 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/sag-p-val351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown