Is CFAP61 p.Arg283Ter (c.847C>T) pathogenic?

CFAP61 p.Arg283Ter (c.847C>T) is classified Pathogenic in CFAP61 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-17). Ultra-rare (popmax 0.0188%, sas); Associated with spermatogenic failure 84.

What condition is associated with CFAP61 p.Arg283Ter (c.847C>T)?

CFAP61 p.Arg283Ter (c.847C>T) is associated with spermatogenic failure 84 (ClinVar).

How common is CFAP61 p.Arg283Ter (c.847C>T) in the general population?

CFAP61 p.Arg283Ter (c.847C>T) is ultra-rare (popmax 0.0188%, sas) (gnomAD).

CFAP61 p.Arg283Ter

c.847C>T · rs201899206 · VCV2504102

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, sas)

Conditions

spermatogenic failure 84

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 8 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP -2.7
Overall
CADD	33.0	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 0.0188% South Asian · 17/90,598 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00981%

Overall 0.00254% 41/1,611,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0188%	5,329
East Asian	0.00669%	14,946
European (non-Finnish)	0.00178%	56,155

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: CFAP61
Protein: p.Arg283Ter
Coding: c.847C>T
MANE Select: NM_015585
dbSNP: rs201899206
Type: single nucleotide variant
Location: chr20:20098802 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB
Residue 283: the 'disordered' region; a UniProt-annotated variant site (in spgf84; pathogenic; no protein detected in patient sperm)

Full CFAP61 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 84 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP61 p.Arg283Gln Likely benign ★ same residue
CFAP61 p.Arg552Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CFAP61 c.3125-1G>C Likely pathogenic ★ same condition
CFAP61 c.143+5G>A Pathogenic same condition
CFAP61 c.144-2A>G Pathogenic same condition
CFAP61 p.Asp971Asn Pathogenic same condition
CFAP61 p.Gly556Arg Pathogenic ⚠ same condition
CFAP61 p.Ile151fs 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/cfap61-p-arg283ter (accessed [today's date]).

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