Is CFH p.Pro1052= (c.3156C>T) pathogenic?

CFH p.Pro1052= (c.3156C>T) is classified Conflicting classifications of pathogenicity in CFH (ClinVar, Conflicting submitters, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 8.48e-05%, nfe); Associated with basal laminar drusen.

What condition is associated with CFH p.Pro1052= (c.3156C>T)?

CFH p.Pro1052= (c.3156C>T) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, age related macular degeneration 4 (ClinVar).

How common is CFH p.Pro1052= (c.3156C>T) in the general population?

CFH p.Pro1052= (c.3156C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CFH p.Pro1052=

c.3156C>T · rs764539113 · VCV875390

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

basal laminar drusen

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 -7	GERP -3.2
Overall
CADD	0.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,916 alleles

Overall 0.000821% 12/1,461,696 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,960
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)grpmax	8.48e-05%	1,179,916

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1052=
Coding: c.3156C>T
MANE Select: NM_000186
dbSNP: rs764539113
Type: single nucleotide variant
Location: chr1:196743474 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1052: the sushi 18 domain; an α-helix; a disulfide bond

Full CFH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

basal laminar drusen — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemolytic uremic syndrome, atypical, susceptibility to, 1 age related macular degeneration 4

Similar variants

CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg232Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg53Cys Pathogenic/Likely pathogenic ★★ same condition
CFH p.Cys431Ser 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-pro1052 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown