Is CFHR5 p.Arg132= (c.394C>A) pathogenic?

CFHR5 p.Arg132= (c.394C>A) is classified Likely benign in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.00401%, afr).

How common is CFHR5 p.Arg132= (c.394C>A) in the general population?

CFHR5 p.Arg132= (c.394C>A) is very rare (popmax 0.00401%, afr) (gnomAD).

CFHR5 p.Arg132=

c.394C>A · rs758371568 · VCV2639698

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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 -14	GERP -3.6
Overall
CADD	0.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,856 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000558% 9/1,613,530 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,952
Remaining individualsnot grpmax-eligible	0.0032%	31,233
European (non-Finnish)	0.000339%	294,948

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: CFHR5
Protein: p.Arg132=
Coding: c.394C>A
MANE Select: NM_030787
dbSNP: rs758371568
Type: single nucleotide variant
Location: chr1:196984101 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 132: a disulfide bond; the sushi 2 domain

Full CFHR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFHR5 p.Arg132Gln Uncertain significance ★★ ⚠ same residue
CFHR5 p.Arg132Trp Uncertain significance ★★ ⚠ same residue
CFHR5 p.Arg132Leu Uncertain significance ★ ⚠ same residue
CFHR5 c.430+5G>T Uncertain significance ★★ same type
CFHR5 c.607+4A>G Uncertain significance ★★ same type
CFHR5 c.608-3T>A Uncertain significance ★★ same type
CFHR5 p.Arg354Gly Uncertain significance ★★ ⚠ same type
CFHR5 p.Arg356Cys Uncertain significance ★★ ⚠ same type

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/cfhr5-p-arg132 (accessed [today's date]).

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