C2 c.-145A>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.2%, eas)
Conditions
2
age related macular degeneration 14
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 | GERP -2.3, phastCons 0.001 |
| Non-coding constraint | Z 4.70 | 1 kb window · o/e 0.68 · regional · uncalibrated |
| Overall | ||
| CADD | 0.751 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.2%
East Asian · 538/44,750 alleles
Filtering AF
1.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.08%
Overall
0.035%
555/1,586,282 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.2% | 83 |
| Remaining individualsnot grpmax-eligible | 0.0163% | 6,122 |
| South Asian | 0.00347% | 28,845 |
| European (non-Finnish) | 0.000342% | 292,197 |
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
- C2
- Coding
- c.-145A>C
- MANE Select
- NM_000063
- dbSNP
- rs150299426
- Type
- single nucleotide variant
- Location
- chr6:31927608 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.61 · 14 PDB
Similar variants
- C2 c.1902+5G>A Uncertain significance ★★ same condition
- C2 p.Arg129His Uncertain significance ★★ ⚠ same condition
- C2 p.Arg734Leu Uncertain significance ★★ ⚠ same condition
- C2 p.Asp390Ala Uncertain significance ★★ ⚠ same condition
- C2 p.Asp661Asn Uncertain significance ★★ ⚠ same condition
- C2 p.Lys572Asn Uncertain significance ★★ ⚠ same condition
- C2 p.Phe273= Uncertain significance ★★ same condition
- C2 p.Phe95Val Uncertain significance ★★ ⚠ same condition
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/c2-c-minus-145a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown