LCA5 p.Ser243=
c.729G>A · rs756379569 · VCV1156925
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -4.5 | GERP -3.5 |
| Overall | ||
| CADD | 1.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,798 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000558%
9/1,612,202 alleles · very rare
exomes 9/1,460,070 · genomes 0/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,798 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,420 |
| European (non-Finnish) | 0.000594% | 168,420 |
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.Ser243=
- Coding
- c.729G>A
- MANE Select
- NM_001122769
- dbSNP
- rs756379569
- Type
- single nucleotide variant
- Location
- chr6:79493742 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.05
Similar variants
- LCA5 p.Ser243Leu 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-ser243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown