Is CFTR p.Pro5= (c.15T>C) pathogenic?

CFTR p.Pro5= (c.15T>C) is classified Likely benign in CFTR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-05). Very rare (popmax 0.00178%, nfe); Associated with cystic fibrosis.

What condition is associated with CFTR p.Pro5= (c.15T>C)?

CFTR p.Pro5= (c.15T>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Pro5= (c.15T>C) in the general population?

CFTR p.Pro5= (c.15T>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Pro5=

c.15T>C · rs751475070 · VCV789399

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

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 -0.86	GERP -3.2, phastCons 0.012
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,864 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00161% 26/1,613,650 alleles · very rare exomes 25/1,461,714 · genomes 1/151,936 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)grpmax	0.00178%	56,184
African / African-American	0.00134%	74,820

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro5=
Coding: c.15T>C
MANE Select: NM_000492
dbSNP: rs751475070
Type: single nucleotide variant
Location: chr7:117480109 (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 5: 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

For Cystic fibrosis (Orphanet):

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

Similar variants

CFTR p.Pro5Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CFTR p.Pro5Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CFTR p.Pro5Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro5 (accessed [today's date]).

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