Is CFAP65 p.Leu527fs (c.1580del) pathogenic?

CFAP65 p.Leu527fs (c.1580del) is classified Pathogenic in CFAP65 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-21). Absent from gnomAD; Associated with spermatogenic failure 40.

What condition is associated with CFAP65 p.Leu527fs (c.1580del)?

CFAP65 p.Leu527fs (c.1580del) is associated with spermatogenic failure 40 (ClinVar).

How common is CFAP65 p.Leu527fs (c.1580del) in the general population?

CFAP65 p.Leu527fs (c.1580del) is absent from gnomAD (gnomAD).

CFAP65 p.Leu527fs

c.1580del · rs1574628422 · VCV694536

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

spermatogenic failure 40

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 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.63	GERP -3.4, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFAP65
Protein: p.Leu527fs
Coding: c.1580del
MANE Select: NM_194302
dbSNP: rs1574628422
Type: Deletion
Location: chr2:219029473 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.03

Full CFAP65 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 40 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP65 p.Ile1450fs Likely pathogenic ★ same condition
CFAP65 c.645+1G>A Pathogenic ★ same condition
CFAP65 p.Glu1781Ter Pathogenic ★ same condition
CFAP65 p.Ala497Thr Uncertain significance ★ ⚠ same condition
CFAP65 p.Arg762Ter Pathogenic same condition
CFAP65 p.Trp892Ter Pathogenic same condition
CFAP65 p.Gly155Ala Uncertain significance ⚠ same condition
CFAP65 p.Pro1477Ser Uncertain significance ⚠ 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/cfap65-p-leu527fs (accessed [today's date]).

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