LCA5 p.Asp633=
c.1899C>T · rs769512467 · VCV1133103
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.125%, eas)
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 1.9 | GERP 1.8, phastCons 0.98 |
| Overall | ||
| CADD | 1.029 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.125%
East Asian · 56/44,892 alleles
Filtering AF
0.0986%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0892%
Overall
0.00409%
66/1,613,830 alleles · rare
exomes 63/1,461,778 · genomes 3/152,052 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.125% | 802 |
| South Asian | 0.00769% | 13,012 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,240 |
| European (non-Finnish) | 8.48e-05% | 1,179,902 |
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.Asp633=
- Coding
- c.1899C>T
- MANE Select
- NM_001122769
- dbSNP
- rs769512467
- Type
- single nucleotide variant
- Location
- chr6:79487199 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.05
- Residue 633
- the 'disordered' region
Similar variants
- LCA5 p.Asp633Asn 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-asp633 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown