CFHR4 p.Thr81=
c.243G>A · rs77556138 · VCV1336563
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.21%, afr)
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 0.044 | GERP -0.79 |
| Overall | ||
| CADD | 2.264 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.21%
African / African-American · 2,379/74,226 alleles
Filtering AF
3.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.05%
Overall
0.167%
2,694/1,610,032 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.21% | 31 |
| Remaining individualsnot grpmax-eligible | 0.22% | 455 |
| Admixed American | 0.205% | 487 |
| Middle Eastern | 0.0827% | 1,209 |
| South Asian | 0.0121% | 8,268 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,788 |
| East Asian | 0.0067% | 14,929 |
| European (non-Finnish) | 0.00289% | 34,632 |
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
- CFHR4
- Protein
- p.Thr81=
- Coding
- c.243G>A
- MANE Select
- NM_001201550
- dbSNP
- rs77556138
- Type
- single nucleotide variant
- Location
- chr1:196902602 (GRCh38)
- Gene constraint
- LOEUF 1.204 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.75
- Residue 81
- the sushi 1 domain
Similar variants
- CFHR4 p.Thr81Met Likely benign ★ ⚠ same residue
- CFHR4 p.Ala159Val Uncertain significance ★★ ⚠ same type
- CFHR4 p.Arg40His Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ile318Thr Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ser199Tyr Uncertain significance ★★ ⚠ same type
- CFHR4 p.Ser507Leu Uncertain significance ★★ ⚠ same type
- CFHR4 p.Trp68Ter Uncertain significance ★★ same type
- CFHR4 p.Tyr238Ser Uncertain significance ★★ ⚠ 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/cfhr4-p-thr81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown