Is CFAP69 p.Arg868Ter (c.2602C>T) pathogenic?

CFAP69 p.Arg868Ter (c.2602C>T) is classified Likely pathogenic in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-17). Very rare (popmax 0.00945%, afr); Associated with Non-syndromic male infertility due to sperm motility disorder.

What condition is associated with CFAP69 p.Arg868Ter (c.2602C>T)?

CFAP69 p.Arg868Ter (c.2602C>T) is associated with Non-syndromic male infertility due to sperm motility disorder (ClinVar).

How common is CFAP69 p.Arg868Ter (c.2602C>T) in the general population?

CFAP69 p.Arg868Ter (c.2602C>T) is very rare (popmax 0.00945%, afr) (gnomAD).

CFAP69 p.Arg868Ter

c.2602C>T · VCV3779058

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 0.00945%, afr)

Conditions

Non-syndromic male infertility due to sperm motility disorder

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 22 of 23
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP 3.3
Overall
CADD	36.0	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 0.00945% African / African-American · 7/74,070 alleles

Filtering AF 0.00467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00427%

Overall 0.0105% 167/1,588,808 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.254%	393
Remaining individualsnot grpmax-eligible	0.026%	3,844
African / African-Americangrpmax	0.00945%	10,581
European (non-Finnish)	0.00582%	17,170
Admixed American	0.00176%	56,780
Finnishnot grpmax-eligible	0.00158%	63,378

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP69
Protein: p.Arg868Ter
Coding: c.2602C>T
MANE Select: NM_001039706
Type: single nucleotide variant
Location: chr7:90309314 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 868: a UniProt-annotated variant site (in spgf24)

Full CFAP69 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Non-syndromic male infertility due to sperm motility disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP69 p.Phe731Leu Uncertain significance ★★ ⚠ same type
CFAP69 p.Tyr819His Uncertain significance ★★ ⚠ same type
CFAP69 c.1857+47T>A Benign ★★ same type
CFAP69 c.682+50A>C Benign ★★ same type
CFAP69 p.Ala12= Benign ★★ same type
CFAP69 p.Ala182= Benign ★★ same type
CFAP69 p.Ala8= Benign/Likely benign ★★ same type
CFAP69 p.Arg106His 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/cfap69-p-arg868ter (accessed [today's date]).

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