Is CFH p.Asp194= (c.582C>T) pathogenic?

CFH p.Asp194= (c.582C>T) is classified Likely benign in CFH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Very rare (popmax 0.00893%, eas); Associated with age related macular degeneration 4.

What condition is associated with CFH p.Asp194= (c.582C>T)?

CFH p.Asp194= (c.582C>T) is associated with age related macular degeneration 4, basal laminar drusen, complement factor H deficiency (ClinVar).

How common is CFH p.Asp194= (c.582C>T) in the general population?

CFH p.Asp194= (c.582C>T) is very rare (popmax 0.00893%, eas) (gnomAD).

CFH p.Asp194=

c.582C>T · rs573136624 · VCV2420168

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Conditions

age related macular degeneration 4

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 -1.4	GERP -2.9
Overall
CADD	1.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,778 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00149% 24/1,612,904 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,194
Admixed American	0.005%	19,985
South Asian	0.0022%	45,525
European (non-Finnish)	0.00127%	78,616

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.Asp194=
Coding: c.582C>T
MANE Select: NM_000186
dbSNP: rs573136624
Type: single nucleotide variant
Location: chr1:196677630 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 194: a disulfide bond; the sushi 3 domain

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

Disease context

Also linked: basal laminar drusen complement factor H deficiency atypical hemolytic-uremic syndrome

Similar variants

CFH p.Asp194Glu Uncertain significance ★ ⚠ same residue
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

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-asp194 (accessed [today's date]).

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