Is CFAP91 p.Ile285fs (c.852del) pathogenic?

CFAP91 p.Ile285fs (c.852del) is classified Likely pathogenic in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). Very rare (popmax 0.00221%, sas); Associated with spermatogenic failure 51.

What condition is associated with CFAP91 p.Ile285fs (c.852del)?

CFAP91 p.Ile285fs (c.852del) is associated with spermatogenic failure 51 (ClinVar).

How common is CFAP91 p.Ile285fs (c.852del) in the general population?

CFAP91 p.Ile285fs (c.852del) is very rare (popmax 0.00221%, sas) (gnomAD).

CFAP91 p.Ile285fs

c.852del · VCV4845825

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Conditions

spermatogenic failure 51

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 7 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,488 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,458,564 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: CFAP91
Protein: p.Ile285fs
Coding: c.852del
MANE Select: NM_033364
Type: Deletion
Location: chr3:119726340 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.20 · 1 PDB

Full CFAP91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 51 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP91 c.359+1G>A Likely pathogenic ★ same condition
CFAP91 p.Gln545Ter Likely pathogenic ★ same condition
CFAP91 p.Asp42His Uncertain significance ★ ⚠ same condition
CFAP91 c.682+1G>A 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/cfap91-p-ile285fs (accessed [today's date]).

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