LCA5 p.Ser41=
c.123T>C · rs1256558722 · VCV1094773
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00153%, nfe)
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 1.2 | GERP -0.99, phastCons 0.19 |
| Overall | ||
| CADD | 1.786 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00153%
European (non-Finnish) · 18/1,180,028 alleles
Filtering AF
0.000953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00112%
18/1,614,064 alleles · very rare
exomes 16/1,461,860 · genomes 2/152,204 · joint denominator
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.Ser41=
- Coding
- c.123T>C
- MANE Select
- NM_001122769
- dbSNP
- rs1256558722
- Type
- single nucleotide variant
- Location
- chr6:79518772 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.05
- Residue 41
- the 'disordered' region
Similar variants
- LCA5 p.Ser41Ala Uncertain significance ⚠ same residue
- LCA5 p.Ser41fs Likely pathogenic ★ 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
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-ser41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown