Is CFAP54 p.Gln649Ter (c.1945C>T) pathogenic?

CFAP54 p.Gln649Ter (c.1945C>T) is classified Likely pathogenic in CFAP54 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Very rare (popmax 0.000632%, nfe); Associated with ciliary dyskinesia, primary, 54.

What condition is associated with CFAP54 p.Gln649Ter (c.1945C>T)?

CFAP54 p.Gln649Ter (c.1945C>T) is associated with ciliary dyskinesia, primary, 54, spermatogenic failure 98 (ClinVar).

How common is CFAP54 p.Gln649Ter (c.1945C>T) in the general population?

CFAP54 p.Gln649Ter (c.1945C>T) is very rare (popmax 0.000632%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CFAP54 p.Gln649Ter

c.1945C>T · VCV4850627

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000632%, nfe)

Conditions

ciliary dyskinesia, primary, 54

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 68
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 2.6, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000632% European (non-Finnish) · 7/1,108,166 alleles

Filtering AF 0.000263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.000538% 7/1,300,026 alleles · very rare

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: CFAP54
Protein: p.Gln649Ter
Coding: c.1945C>T
MANE Select: NM_001306084
Type: single nucleotide variant
Location: chr12:96540855 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)

Full CFAP54 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spermatogenic failure 98

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CFAP54 p.Arg1629Cys Pathogenic same condition
CFAP54 p.Arg293His Pathogenic same condition
CFAP54 p.Arg319Cys Pathogenic same condition
CFAP54 p.Gly313Arg Pathogenic same condition
CFAP54 p.Cys1993fs Pathogenic ★ same condition
CFAP54 p.Leu2882fs Likely pathogenic ★ same condition
CFAP54 p.Phe1106fs Pathogenic same condition
CFAP54 p.Pro22= Likely benign ★★ same type

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/cfap54-p-gln649ter (accessed [today's date]).

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