CFHR1 p.Ser65=
c.195A>C · rs41305054 · VCV1336493
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, amr)
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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 0.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
Admixed American · 10/57,896 alleles
Filtering AF
0.0093%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00704%
Overall
0.00105%
16/1,525,214 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0173% | 5,790 |
| African / African-American | 0.00513% | 19,497 |
| South Asian | 0.00249% | 40,138 |
| European (non-Finnish) | 8.86e-05% | 1,129,230 |
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
- CFHR1
- Protein
- p.Ser65=
- Coding
- c.195A>C
- MANE Select
- NM_002113
- dbSNP
- rs41305054
- Type
- single nucleotide variant
- Location
- chr1:196825613 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.21 · 2 PDB
- Residue 65
- a disulfide bond; the sushi 1 domain
Similar variants
- CFHR1 p.Asp218Asn Uncertain significance ★★ ⚠ same type
- CFHR1 p.Gln44Ter Uncertain significance ★★ same type
- CFHR1 p.Ile214Asn Uncertain significance ★★ ⚠ same type
- CFHR1 p.Ile70Val Uncertain significance ★★ ⚠ same type
- CFHR1 p.Pro223Leu Uncertain significance ★★ ⚠ same type
- CFHR1 p.Tyr304Cys Uncertain significance ★★ ⚠ same type
- CFHR1 c.253+108G>C Benign ★★ same type
- CFHR1 c.253+213G>A Benign ★★ 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/cfhr1-p-ser65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown