Is CFH p.Ala301fs (c.901del) pathogenic?

CFH p.Ala301fs (c.901del) is classified Pathogenic in CFH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). Very rare (popmax 0.00017%, nfe); Associated with age related macular degeneration 4.

What condition is associated with CFH p.Ala301fs (c.901del)?

CFH p.Ala301fs (c.901del) is associated with age related macular degeneration 4 (ClinVar).

How common is CFH p.Ala301fs (c.901del) in the general population?

CFH p.Ala301fs (c.901del) is very rare (popmax 0.00017%, nfe) (gnomAD).

CFH p.Ala301fs

c.901del · VCV4291652

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

age related macular degeneration 4

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 7 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.14	GERP -3.4

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,408 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,014 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFH
Protein: p.Ala301fs
Coding: c.901del
MANE Select: NM_000186
Type: Deletion
Location: chr1:196685174 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 301: a disulfide bond; the sushi 5 domain

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

Disease context

age related macular degeneration 4 — 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.Ile184fs Pathogenic ★ same condition
CFH c.1697-17_1697-8del Uncertain significance ★ same condition
CFH p.Phe723_Ile726del Uncertain significance ★ same condition
CFH c.3311-59del Benign ★ same condition
CFH c.427+116del Likely benign ★ 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-ala301fs (accessed [today's date]).

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