LCA5 p.Ala153=
c.459C>T · rs112915515 · VCV1099330
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0945%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.62 | phastCons 0.054 |
| Overall | ||
| CADD | 7.516 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0945%
South Asian · 86/91,038 alleles
Filtering AF
0.0783%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0723%
Overall
0.00775%
125/1,613,482 alleles · ultra-rare
exomes 113/1,461,698 · genomes 12/151,784 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0945% | 1,059 |
| Middle Eastern | 0.033% | 3,027 |
| African / African-American | 0.0214% | 4,679 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,250 |
| European (non-Finnish) | 0.000932% | 107,256 |
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
- LCA5
- Protein
- p.Ala153=
- Coding
- c.459C>T
- MANE Select
- NM_001122769
- dbSNP
- rs112915515
- Type
- single nucleotide variant
- Location
- chr6:79513473 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.05
Similar variants
- LCA5 p.Ala153Val Uncertain significance ★ ⚠ same residue
- LCA5 c.190+1G>A Pathogenic/Likely pathogenic ★★ same type
- LCA5 c.721-1G>A Pathogenic/Likely pathogenic ★★ same type
- LCA5 c.721-2A>T Pathogenic/Likely pathogenic ★★ same type
- LCA5 c.858+1G>C Likely pathogenic ★★ same type
- LCA5 p.Ala319Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- LCA5 p.Arg218Ter Pathogenic/Likely pathogenic ★★ same type
- LCA5 p.Arg255Ter 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/lca5-p-ala153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown