Is CFHR5 p.Trp256Ter (c.767G>A) pathogenic?

CFHR5 p.Trp256Ter (c.767G>A) is classified Uncertain significance in CFHR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). Very rare (popmax 0.00669%, eas); Associated with C3 glomerulonephritis.

What condition is associated with CFHR5 p.Trp256Ter (c.767G>A)?

CFHR5 p.Trp256Ter (c.767G>A) is associated with C3 glomerulonephritis (ClinVar).

How common is CFHR5 p.Trp256Ter (c.767G>A) in the general population?

CFHR5 p.Trp256Ter (c.767G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

CFHR5 p.Trp256Ter

c.767G>A · VCV3575877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

C3 glomerulonephritis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Overall
CADD	38.0	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 0.00669% East Asian · 3/44,818 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000558% 9/1,613,156 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,939
Remaining individualsnot grpmax-eligible	0.0048%	20,823
South Asian	0.00329%	30,351

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.Trp256Ter
Coding: c.767G>A
MANE Select: NM_030787
Type: single nucleotide variant
Location: chr1:196995876 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 256: a disulfide bond; 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-trp256ter (accessed [today's date]).

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