Is CFHR5 p.Asn299fs (c.896dup) pathogenic?

CFHR5 p.Asn299fs (c.896dup) is classified Uncertain significance in CFHR5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Very rare (popmax 0.00267%, afr).

How common is CFHR5 p.Asn299fs (c.896dup) in the general population?

CFHR5 p.Asn299fs (c.896dup) is very rare (popmax 0.00267%, afr) (gnomAD).

CFHR5 p.Asn299fs

c.896dup · rs1233073714 · VCV633663

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.3	GERP -3.7
Overall
CADD	16.03	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 0.00267% African / African-American · 2/74,810 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,611,840 alleles · very rare

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.Asn299fs
Coding: c.896dup
MANE Select: NM_030787
dbSNP: rs1233073714
Type: Duplication
Location: chr1:196996124 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.76
Residue 299: a disulfide bond; the sushi 5 domain

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

Similar variants

CFHR5 p.Arg385fs Uncertain significance ★★ same type
CFHR5 p.Asn178fs Uncertain significance ★★ same type
CFHR5 c.254-2_266dup Conflicting classifications of pathogenicity ★ same type
CFHR5 p.Glu163fs Conflicting classifications of pathogenicity ★ same type
CFHR5 p.Glu19fs Uncertain significance ★ same type
CFHR5 p.Ser43fs Uncertain significance ★ same type
CFHR5 p.Tyr468fs Uncertain significance ★ same type
CFHR5 c.(58+1_59-1 Pathogenic same type

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-asn299fs (accessed [today's date]).

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