Is CFAP251 p.Asp42fs (c.123del) pathogenic?

CFAP251 p.Asp42fs (c.123del) is classified Pathogenic in CFAP251 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-03-04). Very rare (popmax 0.0033%, sas); Associated with spermatogenic failure 33.

What condition is associated with CFAP251 p.Asp42fs (c.123del)?

CFAP251 p.Asp42fs (c.123del) is associated with spermatogenic failure 33, male infertility with teratozoospermia due to single gene mutation (ClinVar).

How common is CFAP251 p.Asp42fs (c.123del) in the general population?

CFAP251 p.Asp42fs (c.123del) is very rare (popmax 0.0033%, sas) (gnomAD).

CFAP251 p.Asp42fs

c.123del · rs749163856 · VCV548450

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

spermatogenic failure 33

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 2 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2	GERP -1.9

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,014 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,461,790 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: CFAP251
Protein: p.Asp42fs
Coding: c.123del
MANE Select: NM_144668
dbSNP: rs749163856
Type: Deletion
Location: chr12:121921425 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.84 · 1 PDB
Residue 42: the 'disordered' region

Full CFAP251 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 33 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: male infertility with teratozoospermia due to single gene mutation

Similar variants

CFAP251 p.Arg644fs Pathogenic ★ same condition
CFAP251 p.Glu68fs Pathogenic ★ same condition
CFAP251 c.3007-4915_3338-930del Pathogenic same condition
CFAP251 p.Leu530fs Pathogenic same condition
CFAP251 p.Arg267Ter Pathogenic ★★ same condition
CFAP251 p.Glu111Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP251 c.-20-2A>C Likely pathogenic ★ same condition
CFAP251 p.Gln129Ter Likely 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/cfap251-p-asp42fs (accessed [today's date]).

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