Is CATSPER1 p.Ser72= (c.216C>T) pathogenic?

CATSPER1 p.Ser72= (c.216C>T) is classified Uncertain significance in CATSPER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.000511%, nfe); Associated with spermatogenic failure 7.

What condition is associated with CATSPER1 p.Ser72= (c.216C>T)?

CATSPER1 p.Ser72= (c.216C>T) is associated with spermatogenic failure 7 (ClinVar).

How common is CATSPER1 p.Ser72= (c.216C>T) in the general population?

CATSPER1 p.Ser72= (c.216C>T) is very rare (popmax 0.000511%, nfe) (gnomAD).

CATSPER1 p.Ser72=

c.216C>T · rs753646396 · VCV877901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000511%, nfe)

Conditions

spermatogenic failure 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	2.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000511% European (non-Finnish) · 6/1,173,318 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000413% 6/1,453,702 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: CATSPER1
Protein: p.Ser72=
Coding: c.216C>T
MANE Select: NM_053054
dbSNP: rs753646396
Type: single nucleotide variant
Location: chr11:66026164 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.10
Residue 72: the 'disordered' region

Full CATSPER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spermatogenic failure 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CATSPER1 c.-8G>A Uncertain significance ★★ same condition
CATSPER1 p.Arg297Gln Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Arg332Gln Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Arg558Trp Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Arg757Cys Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Gln324Glu Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Ile486Lys Uncertain significance ★★ ⚠ same condition
CATSPER1 p.Ile583Ser 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/catsper1-p-ser72 (accessed [today's date]).

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