Is CFHR5 p.Ser128= (c.384G>T) pathogenic?

CFHR5 p.Ser128= (c.384G>T) is classified Benign/Likely benign in CFHR5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-22). Rare (popmax 0.457%, afr); Associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II.

How common is CFHR5 p.Ser128= (c.384G>T) in the general population?

CFHR5 p.Ser128= (c.384G>T) is rare (popmax 0.457%, afr) (gnomAD).

CFHR5 p.Ser128=

Q: What condition is associated with CFHR5 p.Ser128= (c.384G>T)?

CFHR5 p.Ser128= (c.384G>T) is associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II (ClinVar).

c.384G>T · rs147791058 · VCV294538

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.457%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.8	GERP -3.6
Overall
CADD	0.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.457% African / African-American · 343/75,002 alleles

Filtering AF 0.417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.034% 549/1,613,740 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.457%	219
Admixed American	0.143%	698
Middle Eastern	0.0991%	1,009
Remaining individualsnot grpmax-eligible	0.0784%	1,275
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,114
European (non-Finnish)	0.00415%	24,078
South Asian	0.0022%	45,528

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.Ser128=
Coding: c.384G>T
MANE Select: NM_030787
dbSNP: rs147791058
Type: single nucleotide variant
Location: chr1:196984091 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 128: a disulfide bond; the sushi 2 domain

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

Disease context

CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFHR5 p.Ser128Leu Uncertain significance ★ ⚠ same residue
CFHR5 p.Arg85Gly Uncertain significance ★★ ⚠ same condition
CFHR5 p.Phe192Leu Uncertain significance ★★ ⚠ same condition
CFHR5 p.Pro26Ser Uncertain significance ★★ ⚠ same condition
CFHR5 p.Val430Ala Uncertain significance ★★ ⚠ same condition
CFHR5 c.254-8T>G Benign/Likely benign ★★ same condition
CFHR5 c.-20T>C Benign/Likely benign ★★ same condition
CFHR5 c.*741T>G Benign ★★ 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-ser128 (accessed [today's date]).

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