Is CFH p.Asn269= (c.807T>C) pathogenic?

CFH p.Asn269= (c.807T>C) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-10). Very rare (popmax 0.00544%, nfe); Associated with basal laminar drusen.

What condition is associated with CFH p.Asn269= (c.807T>C)?

CFH p.Asn269= (c.807T>C) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

How common is CFH p.Asn269= (c.807T>C) in the general population?

CFH p.Asn269= (c.807T>C) is very rare (popmax 0.00544%, nfe) (gnomAD).

CFH p.Asn269=

c.807T>C · rs757654697 · VCV1576560

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00544%, nfe)

Conditions

basal laminar drusen

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.84, phastCons 0.15
Overall
CADD	5.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00544% European (non-Finnish) · 64/1,176,516 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.00441% 71/1,609,790 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00544%	18,383
African / African-American	0.00535%	18,694
Remaining individualsnot grpmax-eligible	0.00321%	31,156
Finnishnot grpmax-eligible	0.00156%	64,030

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.Asn269=
Coding: c.807T>C
MANE Select: NM_000186
dbSNP: rs757654697
Type: single nucleotide variant
Location: chr1:196685080 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 269: a disulfide bond; the sushi 5 domain

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

Disease context

basal laminar drusen — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemolytic uremic syndrome, atypical, susceptibility to, 1 complement factor H deficiency age related macular degeneration 4

Similar variants

CFH p.Asn269Tyr Uncertain significance ★ ⚠ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.350+1G>T Pathogenic/Likely pathogenic ★★ same condition
CFH c.619+1G>A Pathogenic/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-asn269 (accessed [today's date]).

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