Is CFH p.Ser1069Pro (c.3205T>C) pathogenic?

CFH p.Ser1069Pro (c.3205T>C) is classified Likely benign in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.0845); Very rare (popmax 6.84e-05%); Associated with Inborn genetic diseases.

What condition is associated with CFH p.Ser1069Pro (c.3205T>C)?

CFH p.Ser1069Pro (c.3205T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CFH p.Ser1069Pro (c.3205T>C) in the general population?

CFH p.Ser1069Pro (c.3205T>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CFH p.Ser1069Pro (c.3205T>C)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

CFH p.Ser1069Pro

c.3205T>C · rs1291043105 · VCV3143797

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.017	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

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,724 alleles · very rare

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.Ser1069Pro
Coding: c.3205T>C
MANE Select: NM_000186
dbSNP: rs1291043105
Type: single nucleotide variant
Location: chr1:196743523 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1069: the sushi 18 domain; a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFH p.Ser1069= Benign/Likely benign ★★ same residue
CFH p.Ala421Thr Uncertain significance ★★ ⚠ same condition
CFH p.Arg53Leu Uncertain significance ★★ ⚠ same condition
CFH p.Asn1050Ile Uncertain significance ★★ ⚠ same condition
CFH p.Asn660His Uncertain significance ★★ ⚠ same condition
CFH p.Asn75His Uncertain significance ★★ ⚠ same condition
CFH p.Asp276Glu Uncertain significance ★★ ⚠ same condition
CFH p.Asp855Asn Uncertain significance ★★ ⚠ 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-ser1069pro (accessed [today's date]).

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