CS p.Leu257=
c.769C>T · rs61738833 · VCV777689
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.48%, nfe)
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 4.5 | GERP -0.67, phastCons 1 |
| Overall | ||
| CADD | 8.202 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.48%
European (non-Finnish) · 17,490/1,180,022 alleles
Filtering AF
1.46%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.46%
Overall
1.22%
19,726/1,614,172 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.48% | 67 |
| Remaining individualsnot grpmax-eligible | 1.28% | 78 |
| Admixed American | 0.975% | 103 |
| Finnishnot grpmax-eligible | 0.792% | 126 |
| Amishnot grpmax-eligible | 0.658% | 152 |
| Middle Eastern | 0.479% | 209 |
| African / African-American | 0.277% | 361 |
| South Asian | 0.109% | 920 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,402 |
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
- CS
- Protein
- p.Leu257=
- Coding
- c.769C>T
- MANE Select
- NM_004077
- dbSNP
- rs61738833
- Type
- single nucleotide variant
- Location
- chr12:56276015 (GRCh38)
- Gene constraint
- LOEUF 0.356 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.56 · 11 PDB
- Residue 257
- an α-helix
Similar variants
- CS p.Phe96= Benign ★★ same type
- CS p.Ala2Gly Uncertain significance ★ ⚠ same type
- CS p.Ala8Ser Uncertain significance ★ ⚠ same type
- CS p.Arg183Gly Uncertain significance ★ ⚠ same type
- CS p.Arg191Gln Uncertain significance ★ ⚠ same type
- CS p.Arg218Gln Uncertain significance ★ ⚠ same type
- CS p.Arg329Gln Uncertain significance ★ ⚠ same type
- CS p.Arg340Gln Uncertain significance ★ ⚠ 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/cs-p-leu257 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown