CFH p.Thr34Pro
c.100A>C · VCV4291343
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2818 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
age related macular degeneration 4
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2818 | likely benign |
|---|---|---|
| REVEL | 0.272 | benign-leaning |
| SaProt | LLR -10.69 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.46 | GERP -4.1 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 28 kb · p 0.84 · regional, not allelic |
| Overall | ||
| CADD | 15.76 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CFH
- Protein
- p.Thr34Pro
- Coding
- c.100A>C
- MANE Select
- NM_000186
- Type
- single nucleotide variant
- Location
- chr1:196673019 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 78.54 · 51 PDB
- Residue 34
- the sushi 1 domain; a disulfide bond
Similar variants
- CFH p.Thr34Arg Uncertain significance ★★ ⚠ same residue
- CFH p.Thr34Ser Uncertain significance ★★ ⚠ same residue
- CFH c.1337-2A>G Likely pathogenic ★★ same condition
- CFH c.2236+1G>C Likely pathogenic ★★ same condition
- CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
- CFH p.Arg53Cys Pathogenic/Likely pathogenic ★★ same condition
- CFH p.Cys431Ser Likely pathogenic ★★ same condition
- CFH p.Cys611Ter Pathogenic/Likely pathogenic ★★ 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/cfh-p-thr34pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown