Is CFH p.Ser1065Arg (c.3193A>C) pathogenic?

CFH p.Ser1065Arg (c.3193A>C) is classified Uncertain significance in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-17). AlphaMissense: likely benign (0.2311); Absent from gnomAD v4.1; Associated with age related macular degeneration 4.

What condition is associated with CFH p.Ser1065Arg (c.3193A>C)?

CFH p.Ser1065Arg (c.3193A>C) is associated with age related macular degeneration 4 (ClinVar).

How common is CFH p.Ser1065Arg (c.3193A>C) in the general population?

CFH p.Ser1065Arg (c.3193A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFH p.Ser1065Arg (c.3193A>C)?

AlphaMissense predicts likely benign (score 0.2311) — an in-silico prediction, not a clinical call.

CFH p.Ser1065Arg

c.3193A>C · VCV4291542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2311 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

age related macular degeneration 4

Computational evidence

Protein change
AlphaMissense	0.2311	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	—	withheld · numbering disagrees past residue 402 · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.1
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Ser1065Arg
Coding: c.3193A>C
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196743511 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1065: the sushi 18 domain; a β-strand

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

Disease context

age related macular degeneration 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
CFH p.Gln859Ter Pathogenic/Likely pathogenic ★★ same condition
CFH p.Glu625Ter 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-ser1065arg (accessed [today's date]).

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