Is CFH p.His878= (c.2634C>T) pathogenic?

CFH p.His878= (c.2634C>T) is classified Benign/Likely benign in CFH (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-04-01). Low-frequency (popmax 2.91%, sas); Associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II.

What condition is associated with CFH p.His878= (c.2634C>T)?

CFH p.His878= (c.2634C>T) is associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II, basal laminar drusen, hemolytic uremic syndrome, atypical, susceptibility to, 1 (ClinVar).

How common is CFH p.His878= (c.2634C>T) in the general population?

CFH p.His878= (c.2634C>T) is low-frequency (popmax 2.91%, sas) (gnomAD).

CFH p.His878=

c.2634C>T · rs35292876 · VCV294504

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.91%, sas)

Conditions

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.28	GERP 0.45, phastCons 0.88
Overall
CADD	3.588	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.91% South Asian · 2,647/91,002 alleles

Filtering AF 2.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.78%

Overall 0.975% 15,718/1,612,918 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.91%	34
Middle Eastern	2.15%	47
Remaining individualsnot grpmax-eligible	0.942%	106
European (non-Finnish)	0.923%	108
Admixed American	0.74%	135
Finnishnot grpmax-eligible	0.699%	143
African / African-American	0.574%	174
Ashkenazi Jewishnot grpmax-eligible	0.467%	214
East Asian	0.00894%	11,182

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.His878=
Coding: c.2634C>T
MANE Select: NM_000186
dbSNP: rs35292876
Type: single nucleotide variant
Location: chr1:196737512 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 878: the sushi 15 domain; a disulfide bond

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

Disease context

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

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-his878 (accessed [today's date]).

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