Is CFHR5 p.Val263= (c.789T>A) pathogenic?

CFHR5 p.Val263= (c.789T>A) is classified Uncertain significance in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). Absent from gnomAD v4.1; Associated with C3 glomerulonephritis.

What condition is associated with CFHR5 p.Val263= (c.789T>A)?

CFHR5 p.Val263= (c.789T>A) is associated with C3 glomerulonephritis (ClinVar).

How common is CFHR5 p.Val263= (c.789T>A) in the general population?

CFHR5 p.Val263= (c.789T>A) is absent from gnomAD v4.1 (gnomAD).

CFHR5 p.Val263=

c.789T>A · VCV3575908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

C3 glomerulonephritis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	donor gain · deltas
Pangolin	Δ0.41	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.065	GERP -0.86, phastCons 0.68
Overall
CADD	16.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFHR5
Protein: p.Val263=
Coding: c.789T>A
MANE Select: NM_030787
Type: single nucleotide variant
Location: chr1:196995898 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 263: the sushi 4 domain

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 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
CFHR5 p.Arg441Cys Uncertain significance ★★ ⚠ same condition
CFHR5 p.Arg85Gly Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn126His Uncertain significance ★★ ⚠ same condition
CFHR5 p.Asn230Asp 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-val263 (accessed [today's date]).

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