Is CFTR p.Phe508= (c.1524T>C) pathogenic?

CFTR p.Phe508= (c.1524T>C) is classified Likely benign in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-05). Very rare (popmax 0.000254%, nfe); Associated with cystic fibrosis.

What condition is associated with CFTR p.Phe508= (c.1524T>C)?

CFTR p.Phe508= (c.1524T>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Phe508= (c.1524T>C) in the general population?

CFTR p.Phe508= (c.1524T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Phe508=

c.1524T>C · rs1400451895 · VCV1774508

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 1.8	GERP 0.5, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,178,890 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,746 alleles · very rare exomes 3/1,460,444 · genomes 0/152,302 · 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.Phe508=
Coding: c.1524T>C
MANE Select: NM_000492
dbSNP: rs1400451895
Type: single nucleotide variant
Location: chr7:117559595 (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 508: a UniProt-annotated variant site (in cf); a UniProt-annotated variant site (in); a UniProt-annotated variant site (in cf and cbavd; most common mutation in caucasian cf chromosomes; impairs protein folding and stability; causes local changes to the surface that mediates interactions between domains; decreases frequency of channel opening in vitro; binds to the cytokeratin-8 and through this binding is primed for the degradation pathway that ends in the proteasome thus impairing trafficking; impairs maturation and trafficking to the cell membrane; impairs recycling to the cell membrane after endocytosis; abolishes marchf2-mediated degradation and); the abc transporter 1 domain

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.Phe508Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CFTR p.Phe508del Pathogenic ★ same residue
CFTR p.Phe508Val Uncertain significance ★★ ⚠ 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-phe508 (accessed [today's date]).

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