Is CFB p.Asp659fs (c.1975_1976del) pathogenic?

CFB p.Asp659fs (c.19751976del) is classified Uncertain significance in CFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). Very rare (popmax 0.000169%, nfe).

How common is CFB p.Asp659fs (c.1975_1976del) in the general population?

CFB p.Asp659fs (c.1975_1976del) is very rare (popmax 0.000169%, nfe) (gnomAD).

CFB p.Asp659fs

c.1975_1976del · rs772068606 · VCV3006872

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP -3.5, phastCons 0.66

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,976 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,808 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: CFB
Protein: p.Asp659fs
Coding: c.1975_1976del
MANE Select: NM_001710
dbSNP: rs772068606
Type: Microsatellite
Location: chr6:31951353 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 28 PDB
Residue 659: an α-helix; a disulfide bond; the peptidase s1 domain

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

Similar variants

CFB p.Asp659Asn Uncertain significance ★ same residue
CFB c.2090-12_2090-10del Uncertain significance ★ same type
CFB p.Ser687fs Uncertain significance ★ same type
CFB c.1168+13CT[2] Likely benign ★ same type
CFB c.897+11_897+13del Likely benign ★ 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/cfb-p-asp659fs (accessed [today's date]).

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