Is CFH p.Glu1172Ala (c.3515A>C) pathogenic?

CFH p.Glu1172Ala (c.3515A>C) is classified Uncertain significance in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2091); Absent from gnomAD v4.1; Associated with atypical hemolytic-uremic syndrome.

What condition is associated with CFH p.Glu1172Ala (c.3515A>C)?

CFH p.Glu1172Ala (c.3515A>C) is associated with atypical hemolytic-uremic syndrome (ClinVar).

How common is CFH p.Glu1172Ala (c.3515A>C) in the general population?

CFH p.Glu1172Ala (c.3515A>C) is absent from gnomAD v4.1 (gnomAD).

How is Atypical hemolytic uremic syndrome inherited?

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

What do computational predictors say about CFH p.Glu1172Ala (c.3515A>C)?

AlphaMissense predicts likely benign (score 0.2091) — an in-silico prediction, not a clinical call.

CFH p.Glu1172Ala

c.3515A>C · VCV4291595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2091 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

atypical hemolytic-uremic syndrome

Computational evidence

Protein change
AlphaMissense	0.2091	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -10.51	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.61, phastCons 0.056
Regional constraint	o/e 0.66	unconstrained · MANE · 3,752 bp · p 4.7e-06 · regional, not allelic
Overall
CADD	19.52	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFH
Protein: p.Glu1172Ala
Coding: c.3515A>C
MANE Select: NM_000186
Type: single nucleotide variant
Location: chr1:196747132 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 1172: the sushi 20 domain; an α-helix; a disulfide bond

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

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.Glu1172Ter Pathogenic ★ same residue
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH p.Arg1215Leu 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

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-glu1172ala (accessed [today's date]).

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