Is CFTR p.Phe640= (c.1920T>C) pathogenic?

CFTR p.Phe640= (c.1920T>C) is classified Conflicting classifications of pathogenicity in CFTR (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-01-29). Rare (popmax 0.127%, amr); Associated with congenital bilateral aplasia of vas deferens from CFTR mutation.

How common is CFTR p.Phe640= (c.1920T>C) in the general population?

CFTR p.Phe640= (c.1920T>C) is rare (popmax 0.127%, amr) (gnomAD).

CFTR p.Phe640=

Q: What condition is associated with CFTR p.Phe640= (c.1920T>C)?

CFTR p.Phe640= (c.1920T>C) is associated with congenital bilateral aplasia of vas deferens from CFTR mutation, cystic fibrosis, CFTR-related disorder (ClinVar).

c.1920T>C · rs145877746 · VCV256250

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

rare (popmax 0.127%, amr)

Conditions

congenital bilateral aplasia of vas deferens from CFTR mutation

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 0.39	GERP -2.9, phastCons 1
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% Admixed American · 76/59,970 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0953%

Overall 0.00638% 103/1,613,558 alleles · rare exomes 47/1,461,252 · genomes 56/152,306 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.127%	789
Remaining individualsnot grpmax-eligible	0.032%	3,124
African / African-American	0.00533%	18,759
European (non-Finnish)	0.000254%	393,261

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.Phe640=
Coding: c.1920T>C
MANE Select: NM_000492
dbSNP: rs145877746
Type: single nucleotide variant
Location: chr7:117592087 (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 640: a UniProt-annotated variant site (in cf); the abc transporter 1 domain; an α-helix

Full CFTR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital bilateral aplasia of vas deferens from CFTR mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cystic fibrosis CFTR-related disorder

Similar variants

CFTR p.Phe640Leu Uncertain significance ★ ⚠ same residue
CFTR p.Phe640Cys 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-phe640 (accessed [today's date]).

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