Is CFH p.Arg232Ter (c.694C>T) pathogenic?

CFH p.Arg232Ter (c.694C>T) is classified Pathogenic/Likely pathogenic in CFH (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-09-17). Very rare (popmax 0.00134%, afr); Associated with complement factor H deficiency.

What condition is associated with CFH p.Arg232Ter (c.694C>T)?

CFH p.Arg232Ter (c.694C>T) is associated with complement factor H deficiency, basal laminar drusen, atypical hemolytic-uremic syndrome (ClinVar).

How common is CFH p.Arg232Ter (c.694C>T) in the general population?

CFH p.Arg232Ter (c.694C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Immunodeficiency with factor H anomaly inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFH p.Arg232Ter

c.694C>T · rs755790570 · VCV1162886

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

complement factor H deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -3.4, phastCons 0.91
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,742 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000994% 16/1,609,276 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,130
Finnishnot grpmax-eligible	0.00156%	63,898
African / African-Americangrpmax	0.00134%	74,742
South Asian	0.0011%	90,918
European (non-Finnish)	0.000935%	106,960

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg232Ter
Coding: c.694C>T
MANE Select: NM_000186
dbSNP: rs755790570
Type: single nucleotide variant
Location: chr1:196679697 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 232: a β-strand; a disulfide bond; the sushi 4 domain

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

Disease context

complement factor H deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal laminar drusen atypical hemolytic-uremic syndrome

For Immunodeficiency with factor H anomaly (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive

Similar variants

CFH p.Arg232Gln Likely pathogenic ★ ⚠ 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-arg232ter (accessed [today's date]).

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