CERS3 p.Tyr253=
c.759T>C · rs374685247 · VCV2958011
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
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 · A>C here scores Δ0.36 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -4.9 |
| Overall | ||
| CADD | 3.816 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,902 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00205%
33/1,613,644 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,451 |
| South Asian | 0.00439% | 22,772 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
| European (non-Finnish) | 0.00212% | 47,185 |
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
- CERS3
- Protein
- p.Tyr253=
- Coding
- c.759T>C
- MANE Select
- NM_001378789
- dbSNP
- rs374685247
- Type
- single nucleotide variant
- Location
- chr15:100469464 (GRCh38)
- Gene constraint
- LOEUF 1.14 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.52
- Residue 253
- the tlc domain
Similar variants
- CERS3 c.466-1G>T Likely pathogenic ★★ same type
- CERS3 p.Arg75Ter Likely pathogenic ★★ same type
- CERS3 p.Arg275Cys Uncertain significance ★★ ⚠ same type
- CERS3 p.Ser177Phe Uncertain significance ★★ ⚠ same type
- CERS3 c.174-81G>A Benign ★★ same type
- CERS3 c.407+74C>T Benign ★★ same type
- CERS3 c.465+65A>T Benign ★★ same type
- CERS3 c.466-110G>T Benign ★★ 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/cers3-p-tyr253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown