Is CFHR5 p.Val110= (c.330A>C) pathogenic?

CFHR5 p.Val110= (c.330A>C) is classified Benign/Likely benign in CFHR5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-22). Low-frequency (popmax 4.56%, afr); Associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II.

How common is CFHR5 p.Val110= (c.330A>C) in the general population?

CFHR5 p.Val110= (c.330A>C) is low-frequency (popmax 4.56%, afr) (gnomAD).

CFHR5 p.Val110=

Q: What condition is associated with CFHR5 p.Val110= (c.330A>C)?

CFHR5 p.Val110= (c.330A>C) is associated with CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II (ClinVar).

c.330A>C · rs61745675 · VCV294537

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.56%, 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 -3.2	GERP -3.5
Overall
CADD	0.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.56% African / African-American · 3,422/74,978 alleles

Filtering AF 4.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.38%

Overall 0.308% 4,961/1,613,088 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.56%	22
Ashkenazi Jewishnot grpmax-eligible	1.58%	63
Middle Eastern	0.611%	164
Remaining individualsnot grpmax-eligible	0.5%	200
Admixed American	0.382%	262
European (non-Finnish)	0.0401%	2,493
South Asian	0.0231%	4,336

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.Val110=
Coding: c.330A>C
MANE Select: NM_030787
dbSNP: rs61745675
Type: single nucleotide variant
Location: chr1:196984037 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 110: 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.Val110Ala Benign/Likely benign ★★ ⚠ 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-val110 (accessed [today's date]).

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