Is CFTR p.Tyr577= (c.1731C>T) pathogenic?

CFTR p.Tyr577= (c.1731C>T) is classified Conflicting classifications of pathogenicity in CFTR (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.028%, nfe); Associated with cystic fibrosis.

What condition is associated with CFTR p.Tyr577= (c.1731C>T)?

CFTR p.Tyr577= (c.1731C>T) is associated with cystic fibrosis, bronchiectasis with or without elevated sweat chloride 1 (ClinVar).

How common is CFTR p.Tyr577= (c.1731C>T) in the general population?

CFTR p.Tyr577= (c.1731C>T) is ultra-rare (popmax 0.028%, nfe) (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Tyr577=

c.1731C>T · rs55928397 · VCV35832

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, nfe)

Conditions

cystic fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.6	GERP -0.89, phastCons 0.001
Overall
CADD	2.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% European (non-Finnish) · 328/1,172,174 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0244%

Overall 0.0227% 364/1,603,002 alleles · ultra-rare exomes 351/1,450,958 · genomes 13/152,044 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.028%	3,574
Admixed American	0.0268%	3,729
Remaining individualsnot grpmax-eligible	0.0194%	5,150
Finnishnot grpmax-eligible	0.0095%	10,528
African / African-American	0.00268%	37,376

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.Tyr577=
Coding: c.1731C>T
MANE Select: NM_000492
dbSNP: rs55928397
Type: single nucleotide variant
Location: chr7:117590404 (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 577: a UniProt-annotated variant site (in cf); the abc transporter 1 domain; a turn

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

Also linked: bronchiectasis with or without elevated sweat chloride 1

For Cystic fibrosis (Orphanet):

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

Similar variants

CFTR p.Tyr577Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
CFTR p.Tyr577Ter 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

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-tyr577 (accessed [today's date]).

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