CFH p.Thr544=
c.1632T>G · rs371443731 · VCV1988449
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00475%, nfe)
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 -12 | GERP -3.7 |
| Overall | ||
| CADD | 0.385 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00475%
European (non-Finnish) · 56/1,179,276 alleles
Filtering AF
0.00375%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00337%
Overall
0.00353%
57/1,612,854 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00475% | 21,058 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,410 |
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
- CFH
- Protein
- p.Thr544=
- Coding
- c.1632T>G
- MANE Select
- NM_000186
- dbSNP
- rs371443731
- Type
- single nucleotide variant
- Location
- chr1:196715705 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 544
- the sushi 9 domain; a disulfide bond
Similar variants
- CFH p.Thr544Ala Uncertain significance ★ ⚠ same residue
- CFH p.Thr544Ile Uncertain significance ★ ⚠ same residue
- CFH c.1337-2A>G Likely pathogenic ★★ same type
- CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same type
- CFH c.2236+1G>C Likely pathogenic ★★ same type
- CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same type
- CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same type
- CFH c.619+1G>A 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/cfh-p-thr544 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown