Is CFH p.Ala415fs (c.1243del) pathogenic?

CFH p.Ala415fs (c.1243del) is classified Pathogenic in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Absent from gnomAD; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFH p.Ala415fs (c.1243del)?

CFH p.Ala415fs (c.1243del) is associated with atypical hemolytic-uremic syndrome, basal laminar drusen (ClinVar).

How common is CFH p.Ala415fs (c.1243del) in the general population?

CFH p.Ala415fs (c.1243del) is absent from gnomAD (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFH p.Ala415fs

c.1243del · rs2149088724 · VCV1452931

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.8	GERP -2.1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFH
Protein: p.Ala415fs
Coding: c.1243del
MANE Select: NM_000186
dbSNP: rs2149088724
Type: Deletion
Location: chr1:196690146 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 415: a β-strand; a disulfide bond; the sushi 7 domain

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

Disease context

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

Also linked: basal laminar drusen

For Atypical hemolytic uremic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CFH p.Gln47fs Likely pathogenic ★★ same condition
CFH p.Phe960fs Pathogenic/Likely pathogenic ★★ same condition
CFH p.Leu750_Lys751del Uncertain significance ★★ same condition
CFH c.245-9del Benign/Likely benign ★★ same condition
CFH c.350+1del Pathogenic ★ same condition
CFH p.Arg885fs Pathogenic ★ same condition
CFH p.Asp748fs Pathogenic ★ same condition
CFH p.Cys16fs 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-ala415fs (accessed [today's date]).

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