Is CFTR p.Pro750= (c.2250T>A) pathogenic?

CFTR p.Pro750= (c.2250T>A) is classified Likely benign in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). Absent from gnomAD v4.1; Associated with cystic fibrosis.

What condition is associated with CFTR p.Pro750= (c.2250T>A)?

CFTR p.Pro750= (c.2250T>A) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Pro750= (c.2250T>A) in the general population?

CFTR p.Pro750= (c.2250T>A) is absent from gnomAD v4.1 (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Pro750=

c.2250T>A · VCV3491591

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.95	GERP -2.5, phastCons 0.003
Overall
CADD	0.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFTR
Protein: p.Pro750=
Coding: c.2250T>A
MANE Select: NM_000492
Type: single nucleotide variant
Location: chr7:117592417 (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 750: a UniProt-annotated variant site (in cf); the 'disordered r region' region

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.Pro750Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CFTR p.Pro750Thr Uncertain significance ★ ⚠ same residue
CFTR p.Pro750fs 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

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-pro750 (accessed [today's date]).

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