CFHR2 p.Cys140=
c.420C>T · rs4085749 · VCV1231528
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 70.3%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.43 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.42 | gain · loss 0.16 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.72 | GERP 1.7, phastCons 0.31 |
| Overall | ||
| CADD | 14.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
70.3%
East Asian · 31,515/44,816 alleles
Filtering AF
69.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 69.4%
Overall
25.2%
407,016/1,613,224 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 70.3% | 1 |
| Admixed American | 47% | 2 |
| Finnishnot grpmax-eligible | 30% | 3 |
| South Asian | 29.4% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 29.1% | 3 |
| Remaining individualsnot grpmax-eligible | 26.5% | 4 |
| European (non-Finnish) | 22.9% | 4 |
| Middle Eastern | 18.6% | 5 |
| Amishnot grpmax-eligible | 13.2% | 8 |
| African / African-American | 5.74% | 17 |
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
- CFHR2
- Protein
- p.Cys140=
- Coding
- c.420C>T
- MANE Select
- NM_005666
- dbSNP
- rs4085749
- Type
- single nucleotide variant
- Location
- chr1:196951018 (GRCh38)
- Gene constraint
- LOEUF 1.498 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.90 · 4 PDB
- Residue 140
- a disulfide bond; the sushi 2 domain
Similar variants
- CFHR2 p.Val16Ala Uncertain significance ★★ ⚠ same type
- CFHR2 c.430+141T>A Benign ★★ same type
- CFHR2 c.430+20C>T Benign ★★ same type
- CFHR2 c.430+7G>A Benign/Likely benign ★★ same type
- CFHR2 c.431-48C>A Benign ★★ same type
- CFHR2 c.431-65C>T Benign ★★ same type
- CFHR2 c.58+129C>G Benign ★★ same type
- CFHR2 c.-65C>G 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/cfhr2-p-cys140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown