Is CFAP69 p.Leu357fs (c.1069_1070insAC) pathogenic?

CFAP69 p.Leu357fs (c.10691070insAC) is classified Pathogenic in CFAP69 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-03). Very rare (popmax 0.00903%, eas); Associated with spermatogenic failure 24.

What condition is associated with CFAP69 p.Leu357fs (c.1069_1070insAC)?

CFAP69 p.Leu357fs (c.1069_1070insAC) is associated with spermatogenic failure 24 (ClinVar).

How common is CFAP69 p.Leu357fs (c.1069_1070insAC) in the general population?

CFAP69 p.Leu357fs (c.1069_1070insAC) is very rare (popmax 0.00903%, eas) (gnomAD).

CFAP69 p.Leu357fs

c.1069_1070insAC · rs764048407 · VCV626908

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00903%, eas)

Conditions

spermatogenic failure 24

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 1.3, phastCons 1
Overall
CADD	28.1	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 0.00903% East Asian · 4/44,274 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00182%

Overall 0.000252% 4/1,589,232 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: CFAP69
Protein: p.Leu357fs
Coding: c.1069_1070insAC
MANE Select: NM_001039706
dbSNP: rs764048407
Type: Insertion
Location: chr7:90277247 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 357: a UniProt-annotated variant site (in spgf24)

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

Disease context

spermatogenic failure 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP69 c.1857+47T>A Benign ★★ same condition
CFAP69 c.682+50A>C Benign ★★ same condition
CFAP69 p.Ser854Arg Benign ★★ same condition
CFAP69 p.Thr885Met Benign ★★ ⚠ same condition
CFAP69 p.Val490Met Benign ★★ same condition
CFAP69 c.860+1G>A Pathogenic same condition
CFAP69 p.Gln255Ter Pathogenic same condition
CFAP69 p.Trp216Ter 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/cfap69-p-leu357fs (accessed [today's date]).

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