Is CFTR p.Arg134= (c.400A>C) pathogenic?

CFTR p.Arg134= (c.400A>C) is classified Likely benign in CFTR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-17). Very rare (popmax 8.48e-05%, nfe); Associated with cystic fibrosis.

What condition is associated with CFTR p.Arg134= (c.400A>C)?

CFTR p.Arg134= (c.400A>C) is associated with cystic fibrosis (ClinVar).

How common is CFTR p.Arg134= (c.400A>C) in the general population?

CFTR p.Arg134= (c.400A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Cystic fibrosis inherited?

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

CFTR p.Arg134=

c.400A>C · rs2485009457 · VCV1736991

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

cystic fibrosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.9	GERP 1.9, phastCons 1
Overall
CADD	12.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,828 alleles

Overall 6.2e-05% 1/1,613,766 alleles · very rare exomes 1/1,461,516 · genomes 0/152,250 · 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.Arg134=
Coding: c.400A>C
MANE Select: NM_000492
dbSNP: rs2485009457
Type: single nucleotide variant
Location: chr7:117531025 (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 134: the abc transmembrane type-1 1 domain; an α-helix

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.Arg134Lys Uncertain significance ★ ⚠ same residue
CFTR p.Arg134Gly 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
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-arg134 (accessed [today's date]).

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