Is CFH p.Pro982= (c.2946A>G) pathogenic?

CFH p.Pro982= (c.2946A>G) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.502%, sas); Associated with basal laminar drusen.

What condition is associated with CFH p.Pro982= (c.2946A>G)?

CFH p.Pro982= (c.2946A>G) is associated with basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1, complement factor H deficiency (ClinVar).

How common is CFH p.Pro982= (c.2946A>G) in the general population?

CFH p.Pro982= (c.2946A>G) is rare (popmax 0.502%, sas) (gnomAD).

CFH p.Pro982=

c.2946A>G · rs553471643 · VCV1563833

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.502%, sas)

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 0.56	GERP 0.56
Overall
CADD	3.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.502% South Asian · 457/91,080 alleles

Filtering AF 0.464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.449%

Overall 0.0292% 471/1,613,992 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.502%	199
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.0144%	6,944
European (non-Finnish)	0.00017%	589,946

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.Pro982=
Coding: c.2946A>G
MANE Select: NM_000186
dbSNP: rs553471643
Type: single nucleotide variant
Location: chr1:196740782 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 982: the sushi 16 domain; 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

Similar variants

CFH p.Pro982Ser Conflicting classifications of pathogenicity ★ same residue
CFH p.Pro982Thr 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

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-pro982 (accessed [today's date]).

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