Is CFH p.Gln47fs (c.139del) pathogenic?

CFH p.Gln47fs (c.139del) is classified Likely pathogenic in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-10). Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Gln47fs (c.139del)?

CFH p.Gln47fs (c.139del) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1, basal laminar drusen, complement factor H deficiency (ClinVar).

CFH p.Gln47fs

c.139del · VCV3575077

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

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 2 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP -0.58, phastCons 0.17

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

Variant & gene context

Gene: CFH
Protein: p.Gln47fs
Coding: c.139del
MANE Select: NM_000186
Type: Deletion
Location: chr1:196673056 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 47: a β-strand; the sushi 1 domain; a disulfide bond

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 p.Ala415fs Pathogenic ★★ same condition
CFH p.Gly247fs 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.Ala1057_Tyr1058insTer Likely pathogenic ★ same condition
CFH p.Ala301fs Pathogenic ★ same condition
CFH p.Ala473fs 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-gln47fs (accessed [today's date]).

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