Is CFH p.Ser1061Pro (c.3181T>C) pathogenic?

CFH p.Ser1061Pro (c.3181T>C) is classified Uncertain significance in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: ambiguous (0.408); Absent from gnomAD v4.1; Associated with basal laminar drusen.

What condition is associated with CFH p.Ser1061Pro (c.3181T>C)?

CFH p.Ser1061Pro (c.3181T>C) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

How common is CFH p.Ser1061Pro (c.3181T>C) in the general population?

CFH p.Ser1061Pro (c.3181T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFH p.Ser1061Pro (c.3181T>C)?

AlphaMissense predicts ambiguous (score 0.408) — an in-silico prediction, not a clinical call.

CFH p.Ser1061Pro

c.3181T>C · VCV3575613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

basal laminar drusen

Computational evidence

Protein change
AlphaMissense	0.408	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -12.92	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.715	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.Ser1061Pro
Coding: c.3181T>C
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196743499 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1061: the sushi 18 domain; 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 complement factor H deficiency age related macular degeneration 4 atypical hemolytic-uremic syndrome

Similar variants

CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/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.Arg1215Leu Likely pathogenic ★★ ⚠ same condition
CFH p.Arg1215Ter 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-ser1061pro (accessed [today's date]).

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