Is CFHR5 p.Arg385fs (c.1153dup) pathogenic?

CFHR5 p.Arg385fs (c.1153dup) is classified Uncertain significance in CFHR5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-08). Ultra-rare (popmax 0.0198%, sas); Associated with C3 glomerulonephritis.

What condition is associated with CFHR5 p.Arg385fs (c.1153dup)?

CFHR5 p.Arg385fs (c.1153dup) is associated with C3 glomerulonephritis (ClinVar).

How common is CFHR5 p.Arg385fs (c.1153dup) in the general population?

CFHR5 p.Arg385fs (c.1153dup) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

CFHR5 p.Arg385fs

c.1153dup · rs746674215 · VCV2729378

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

C3 glomerulonephritis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 1.7, phastCons 0.88
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 0.0198% South Asian · 18/90,822 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00149% 24/1,610,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,046
African / African-American	0.00536%	18,666
Remaining individualsnot grpmax-eligible	0.0016%	62,316
European (non-Finnish)	8.49e-05%	1,177,223

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.Arg385fs
Coding: c.1153dup
MANE Select: NM_030787
dbSNP: rs746674215
Type: Duplication
Location: chr1:197002481 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76

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

Disease context

C3 glomerulonephritis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFHR5 p.Arg385Ser Benign/Likely benign ★★ same residue
CFHR5 p.Ser43fs Uncertain significance ★ same condition
CFHR5 p.Tyr468fs Uncertain significance ★ same condition
CFHR5 c.59-1806_430+3225dup Pathogenic same condition
CFHR5 c.607+4A>G Uncertain significance ★★ same condition
CFHR5 p.Arg132Trp Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg354Gly Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg435Gln Uncertain significance ★★ ⚠ 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/cfhr5-p-arg385fs (accessed [today's date]).

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