Is CFTR p.Ala559fs (c.1674del) pathogenic?

CFTR p.Ala559fs (c.1674del) is classified Pathogenic in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-29). No gnomAD frequency available for this variant; Associated with cystic fibrosis.

What condition is associated with CFTR p.Ala559fs (c.1674del)?

CFTR p.Ala559fs (c.1674del) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Ala559fs (c.1674del) in the general population?

CFTR p.Ala559fs (c.1674del) is no gnomAD frequency available for this variant (gnomAD).

How is Cystic fibrosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CFTR p.Ala559fs

c.1674del · rs397508258 · VCV53327

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

cystic fibrosis

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 12 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFTR
Protein: p.Ala559fs
Coding: c.1674del
MANE Select: NM_000492
dbSNP: rs397508258
Type: Deletion
Location: chr7:117587828 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 60 PDB
Residue 559: a UniProt-annotated variant site (in cf); a UniProt-annotated variant site (in cf; impaired maturation of glycan chains); the abc transporter 1 domain; an α-helix

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

Disease context

cystic fibrosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cystic fibrosis (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CFTR p.Ala559Thr Pathogenic ★★★ same residue
CFTR p.Ala559Pro Pathogenic/Likely pathogenic ★★ same residue
CFTR p.Ala559Ser Uncertain significance ★ ⚠ same residue
CFTR p.Lys1177fs Pathogenic ★★★★ same condition
CFTR c.(?_1 Pathogenic ★★★ same condition
CFTR c.1211del Pathogenic ★★★ same condition
CFTR c.(1584+1_1585-1 Pathogenic ★★★ same condition
CFTR c.(164+1_165-1 Pathogenic ★★★ 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/cftr-p-ala559fs (accessed [today's date]).

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