Is CFH p.Ile808Met (c.2424A>G) pathogenic?

CFH p.Ile808Met (c.2424A>G) is classified Conflicting classifications of pathogenicity in CFH (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-15). AlphaMissense: likely benign (0.0849); Ultra-rare (popmax 0.0748%, amr); Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Ile808Met (c.2424A>G)?

CFH p.Ile808Met (c.2424A>G) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1, basal laminar drusen, complement factor H deficiency (ClinVar).

How common is CFH p.Ile808Met (c.2424A>G) in the general population?

CFH p.Ile808Met (c.2424A>G) is ultra-rare (popmax 0.0748%, amr) (gnomAD).

What do computational predictors say about CFH p.Ile808Met (c.2424A>G)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

CFH p.Ile808Met

c.2424A>G · rs752302466 · VCV875193

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0748%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.017	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 -1.6	GERP -0.84
Regional constraint	o/e 1.01	unconstrained · MANE · 53 kb · p 0.76 · regional, not allelic
Overall
CADD	1.087	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0748% Admixed American · 37/49,460 alleles

Filtering AF 0.0558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0491%

Overall 0.00266% 38/1,429,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0748%	1,337
Remaining individualsnot grpmax-eligible	0.00186%	53,716

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.Ile808Met
Coding: c.2424A>G
MANE Select: NM_000186
dbSNP: rs752302466
Type: single nucleotide variant
Location: chr1:196736834 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB

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

Disease context

hemolytic uremic syndrome, atypical, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal laminar drusen complement factor H deficiency 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-ile808met (accessed [today's date]).

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