Is CFH p.Gln672= (c.2016A>G) pathogenic?

CFH p.Gln672= (c.2016A>G) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with basal laminar drusen.

What condition is associated with CFH p.Gln672= (c.2016A>G)?

CFH p.Gln672= (c.2016A>G) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

CFH p.Gln672=

Q: How common is CFH p.Gln672= (c.2016A>G) in the general population?

CFH p.Gln672= (c.2016A>G) is common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2016A>G · rs3753396 · VCV294498

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 48.1%, eas) — too common for a highly-penetrant pathogenic allele

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 -3.7	GERP -3.7
Overall
CADD	3.433	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.1% East Asian · 21,491/44,708 alleles

Filtering AF 47.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.3%

Overall 17.4% 280,291/1,608,810 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	48.1%	2
Admixed American	30.7%	3
Amishnot grpmax-eligible	25.7%	4
Remaining individualsnot grpmax-eligible	17.3%	6
European (non-Finnish)	16.9%	6
Middle Eastern	14.9%	7
South Asian	14.2%	7
Finnishnot grpmax-eligible	14.1%	7
Ashkenazi Jewishnot grpmax-eligible	12.1%	8
African / African-American	5.56%	18

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.Gln672=
Coding: c.2016A>G
MANE Select: NM_000186
dbSNP: rs3753396
Type: single nucleotide variant
Location: chr1:196726612 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 672: the sushi 11 domain; a β-strand; a disulfide bond

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 atypical hemolytic-uremic syndrome focal segmental glomerulosclerosis

Similar variants

CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>A Pathogenic/Likely pathogenic ★★ same condition
CFH c.2236+1G>C Likely pathogenic ★★ same condition
CFH c.3493+1G>A Pathogenic/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.Arg1215Leu Likely pathogenic ★★ same condition
CFH p.Arg1215Ter 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-gln672 (accessed [today's date]).

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