Is CFH p.Pro440fs (c.1318_1327del) pathogenic?

CFH p.Pro440fs (c.13181327del) is classified Pathogenic in CFH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-04-18). Absent from gnomAD; Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Pro440fs (c.1318_1327del)?

CFH p.Pro440fs (c.1318_1327del) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Pro440fs (c.1318_1327del) in the general population?

CFH p.Pro440fs (c.1318_1327del) is absent from gnomAD (gnomAD).

CFH p.Pro440fs

c.1318_1327del · rs1558162157 · VCV599109

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 9 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.6	GERP -3.5
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.Pro440fs
Coding: c.1318_1327del
MANE Select: NM_000186
dbSNP: rs1558162157
Type: Deletion
Location: chr1:196690221 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 440: a disulfide bond; the sushi 7 domain

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

Similar variants

CFH p.Gln47fs Likely pathogenic ★★ same condition
CFH p.Leu750_Lys751del Uncertain significance ★★ same condition
CFH c.245-9del Benign/Likely benign ★★ same condition
CFH p.Ala1057_Tyr1058insTer Likely pathogenic ★ same condition
CFH p.His537fs Pathogenic ★ same condition
CFH p.Phe723_Ile726del Uncertain significance ★ same condition
CFH p.Pro440Arg Uncertain significance ★ ⚠ same residue
CFH p.Pro440Ser Uncertain significance ★ same residue

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-pro440fs (accessed [today's date]).

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