Is CFTR p.Lys593= (c.1779A>G) pathogenic?

CFTR p.Lys593= (c.1779A>G) is classified Likely benign in CFTR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-04). Very rare (popmax 0.00701%, sas); Associated with cystic fibrosis.

What condition is associated with CFTR p.Lys593= (c.1779A>G)?

CFTR p.Lys593= (c.1779A>G) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Lys593= (c.1779A>G) in the general population?

CFTR p.Lys593= (c.1779A>G) is very rare (popmax 0.00701%, sas) (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Lys593=

c.1779A>G · rs1217712466 · VCV1628860

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00701%, sas)

Conditions

cystic fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.56, phastCons 1
Overall
CADD	6.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00701% South Asian · 6/85,570 alleles

Filtering AF 0.00302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00205%

Overall 0.000379% 6/1,582,520 alleles · very rare exomes 6/1,430,178 · genomes 0/152,342 · joint denominator

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: CFTR
Protein: p.Lys593=
Coding: c.1779A>G
MANE Select: NM_000492
dbSNP: rs1217712466
Type: single nucleotide variant
Location: chr7:117591946 (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 593: a UniProt-annotated variant site (in cf); 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.Lys593fs Likely pathogenic ★ same residue
CFTR c.1585-1G>A Pathogenic ★★★★ same condition
CFTR c.1766+1G>A Pathogenic ★★★★ same condition
CFTR c.2657+5G>A Pathogenic ★★★★ same condition
CFTR c.2988+1G>A Pathogenic ★★★★ same condition
CFTR c.3718-2477C>T Pathogenic ★★★★ same condition
CFTR c.489+1G>T Pathogenic ★★★★ same condition
CFTR c.579+1G>T 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-lys593 (accessed [today's date]).

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