Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.98%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -3.9 |
| Overall | ||
| CADD | 1.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.98%
African / African-American · 5,231/74,942 alleles
Filtering AF
6.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.76%
Overall
0.379%
6,109/1,613,740 alleles · common
exomes 3,050/1,461,532 · genomes 3,059/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.98% | 14 |
| Admixed American | 0.606% | 165 |
| Remaining individualsnot grpmax-eligible | 0.536% | 187 |
| Middle Eastern | 0.248% | 403 |
| South Asian | 0.0187% | 5,357 |
| European (non-Finnish) | 0.0125% | 8,026 |
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
- CERS2
- Protein
- p.Tyr254=
- Coding
- c.762C>T
- MANE Select
- NM_022075
- dbSNP
- rs9435954
- Type
- single nucleotide variant
- Location
- chr1:150966842 (GRCh38)
- Gene constraint
- LOEUF 0.501 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 87.31
- Residue 254
- the tlc domain
Similar variants
- CERS2 p.Tyr254Cys Uncertain significance ★ ⚠ same residue
- CERS2 p.Ala152= Benign ★★ same type
- CERS2 p.Ser199= Benign ★★ same type
- CERS2 p.Ala23Ser Uncertain significance ★ ⚠ same type
- CERS2 p.Ala23Val Uncertain significance ★ ⚠ same type
- CERS2 p.Ala34Thr Uncertain significance ★ same type
- CERS2 p.Ala46Gly Uncertain significance ★ ⚠ same type
- CERS2 p.Arg105Leu 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/cers2-p-tyr254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown