Is CFTR p.Leu796Pro (c.2387T>C) pathogenic?

CFTR p.Leu796Pro (c.2387T>C) is classified Uncertain significance in CFTR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1469); Very rare (popmax 0.00453%, eas); Associated with cystic fibrosis.

What condition is associated with CFTR p.Leu796Pro (c.2387T>C)?

CFTR p.Leu796Pro (c.2387T>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Leu796Pro (c.2387T>C) in the general population?

CFTR p.Leu796Pro (c.2387T>C) is very rare (popmax 0.00453%, eas) (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.Leu796Pro (c.2387T>C)?

AlphaMissense predicts likely benign (score 0.1469) — an in-silico prediction, not a clinical call.

CFTR p.Leu796Pro

c.2387T>C · rs1291965190 · VCV860104

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00453%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cystic fibrosis

Computational evidence

Protein change
AlphaMissense	0.1469	likely benign
REVEL	0.662	pathogenic-leaning
SaProt	LLR -10.28	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 187 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.00453% East Asian · 2/44,104 alleles

Filtering AF 0.000752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000281%

Overall 0.000131% 2/1,521,192 alleles · very rare exomes 2/1,368,884 · genomes 0/152,308 · 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.Leu796Pro
Coding: c.2387T>C
MANE Select: NM_000492
dbSNP: rs1291965190
Type: single nucleotide variant
Location: chr7:117592554 (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 796: 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.Leu796Gln Uncertain significance ★ ⚠ same residue
CFTR p.Leu796= Likely benign ★ 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-leu796pro (accessed [today's date]).

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