Is CFAP44 p.Arg224Ter (c.670C>T) pathogenic?

CFAP44 p.Arg224Ter (c.670C>T) is classified Likely pathogenic in CFAP44 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.00273%, nfe); Associated with spermatogenic failure 20.

What condition is associated with CFAP44 p.Arg224Ter (c.670C>T)?

CFAP44 p.Arg224Ter (c.670C>T) is associated with spermatogenic failure 20 (ClinVar).

How common is CFAP44 p.Arg224Ter (c.670C>T) in the general population?

CFAP44 p.Arg224Ter (c.670C>T) is very rare (popmax 0.00273%, nfe) (gnomAD).

CFAP44 p.Arg224Ter

c.670C>T · rs768429457 · VCV1339091

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 0.00273%, nfe)

Conditions

spermatogenic failure 20

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 6 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 2.4, phastCons 1
Overall
CADD	37.0	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 0.00273% European (non-Finnish) · 32/1,170,842 alleles

Filtering AF 0.00198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00262% 42/1,601,170 alleles · very rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.658%	152
European (non-Finnish)grpmax	0.00273%	36,589
East Asian	0.00224%	44,674
Remaining individualsnot grpmax-eligible	0.00161%	62,036
African / African-American	0.00134%	74,430
South Asian	0.00111%	89,848

Amish 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: CFAP44
Protein: p.Arg224Ter
Coding: c.670C>T
MANE Select: NM_001164496
dbSNP: rs768429457
Type: single nucleotide variant
Location: chr3:113416528 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87 · 1 PDB

Full CFAP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP44 p.Glu463Ter Pathogenic ★★ same condition
CFAP44 c.408-2A>T Likely pathogenic ★ same condition
CFAP44 c.5078-2A>G Likely pathogenic ★ same condition
CFAP44 p.Gly435Ter Likely pathogenic ★ same condition
CFAP44 p.Ser106Pro Uncertain significance ★ ⚠ same condition
CFAP44 p.Tyr546His Uncertain significance ★ ⚠ same condition
CFAP44 p.Arg1059Ter Pathogenic same condition
CFAP44 p.Leu590Gln 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/cfap44-p-arg224ter (accessed [today's date]).

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