Is CFH p.Ser1158fs (c.3472dup) pathogenic?

CFH p.Ser1158fs (c.3472dup) is classified Likely pathogenic in CFH (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Ser1158fs (c.3472dup)?

CFH p.Ser1158fs (c.3472dup) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.Ser1158fs (c.3472dup) in the general population?

CFH p.Ser1158fs (c.3472dup) is absent from gnomAD (gnomAD).

CFH p.Ser1158fs

c.3472dup · rs2529557310 · VCV3241995

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (21 of 22, 22 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.4	GERP 1.8, phastCons 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.Ser1158fs
Coding: c.3472dup
MANE Select: NM_000186
dbSNP: rs2529557310
Type: Duplication
Location: chr1:196745977 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1158: the sushi 19 domain; an α-helix; 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

Similar variants

CFH p.Ser1158Pro Uncertain significance ★ ⚠ same residue
CFH p.Ile868fs Pathogenic/Likely pathogenic ★★ same condition
CFH c.245-10_245-9dup Benign/Likely benign ★★ same condition
CFH c.245-11_245-9dup Benign/Likely benign ★★ same condition
CFH c.245-9dup Benign/Likely benign ★★ same condition
CFH c.2783-3dup Benign/Likely benign ★★ same condition
CFH p.Tyr829fs Pathogenic ★ same condition
CFH p.Gln846fs 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-ser1158fs (accessed [today's date]).

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