Is CFTR p.Ser50Pro (c.148T>C) pathogenic?

CFTR p.Ser50Pro (c.148T>C) is classified Pathogenic/Likely pathogenic in CFTR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-25). AlphaMissense: likely pathogenic (0.9639); No allele count reported in gnomAD v4.1 (AN 1,582,680); Associated with cystic fibrosis.

What condition is associated with CFTR p.Ser50Pro (c.148T>C)?

CFTR p.Ser50Pro (c.148T>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Ser50Pro (c.148T>C) in the general population?

CFTR p.Ser50Pro (c.148T>C) is no allele count reported in gnomAD v4.1 (AN 1,582,680) (gnomAD).

How is Cystic fibrosis inherited?

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

What do computational predictors say about CFTR p.Ser50Pro (c.148T>C)?

AlphaMissense predicts likely pathogenic (score 0.9639) — an in-silico prediction, not a clinical call.

CFTR p.Ser50Pro

c.148T>C · rs397508217 · VCV53266

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9639 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,680)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cystic fibrosis

Computational evidence

Protein change
AlphaMissense	0.9639	likely pathogenic ✓ concordant with ClinVar · top 5% in CFTR
REVEL	0.811	moderately pathogenic-leaning
SaProt	LLR -12.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 187 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,582,680). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFTR
Protein: p.Ser50Pro
Coding: c.148T>C
MANE Select: NM_000492
dbSNP: rs397508217
Type: single nucleotide variant
Location: chr7:117504347 (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 50: an α-helix; a UniProt-annotated variant site (in cbavd)

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.Ser50= Likely benign ★★ same residue
CFTR p.Ser50Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
CFTR p.Ser50fs 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-ser50pro (accessed [today's date]).

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