Is CFH p.Arg53Cys (c.157C>T) pathogenic?

CFH p.Arg53Cys (c.157C>T) is classified Pathogenic/Likely pathogenic in CFH (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-09-17). AlphaMissense: likely pathogenic (0.8711); Very rare (popmax 0.00439%, sas); Associated with hemolytic uremic syndrome, atypical, susceptibility to, 1.

What condition is associated with CFH p.Arg53Cys (c.157C>T)?

CFH p.Arg53Cys (c.157C>T) is associated with hemolytic uremic syndrome, atypical, susceptibility to, 1, basal laminar drusen, complement factor H deficiency (ClinVar).

How common is CFH p.Arg53Cys (c.157C>T) in the general population?

CFH p.Arg53Cys (c.157C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CFH p.Arg53Cys (c.157C>T)?

AlphaMissense predicts likely pathogenic (score 0.8711) — an in-silico prediction, not a clinical call.

CFH p.Arg53Cys

c.157C>T · rs757785149 · VCV1068249

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.8711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hemolytic uremic syndrome, atypical, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.8711	likely pathogenic ✓ concordant with ClinVar
REVEL	0.501	indeterminate
SaProt	LLR -13.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.28, phastCons 0.83
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.84 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,070 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00118% 19/1,613,678 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.0011%	90,756

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.Arg53Cys
Coding: c.157C>T
MANE Select: NM_000186
dbSNP: rs757785149
Type: single nucleotide variant
Location: chr1:196673076 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.54 · 51 PDB
Residue 53: the sushi 1 domain; a disulfide bond

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

Disease context

hemolytic uremic syndrome, atypical, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

CFH p.Arg53Leu Uncertain significance ★★ same residue
CFH p.Arg53Ser Likely pathogenic ★ ⚠ same residue
CFH p.Arg53Gly Uncertain significance ★ ⚠ same residue
CFH p.Arg53His Conflicting classifications of pathogenicity ★ ⚠ same residue
CFH p.Arg53Pro Uncertain significance ★ ⚠ same residue
CFH p.Arg53= Likely benign ★ same residue
CFH c.1337-2A>G Likely pathogenic ★★ same condition
CFH c.1520-1G>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-arg53cys (accessed [today's date]).

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