Is CSPP1 p.Arg218Ter (c.652C>T) pathogenic?

CSPP1 p.Arg218Ter (c.652C>T) is classified Likely pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-27). Very rare (popmax 0.00223%, eas); Associated with CSPP1-related disorder.

What condition is associated with CSPP1 p.Arg218Ter (c.652C>T)?

CSPP1 p.Arg218Ter (c.652C>T) is associated with CSPP1-related disorder (ClinVar).

How common is CSPP1 p.Arg218Ter (c.652C>T) in the general population?

CSPP1 p.Arg218Ter (c.652C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CSPP1 p.Arg218Ter

c.652C>T · VCV4900715

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 0.00223%, eas)

Conditions

CSPP1-related disorder

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 7 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 0.99
Overall
CADD	36.0	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 0.00223% East Asian · 1/44,822 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,758 alleles · very rare exomes 3/1,461,534 · genomes 0/151,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,822
European (non-Finnish)	0.00017%	589,859

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: CSPP1
Protein: p.Arg218Ter
Coding: c.652C>T
MANE Select: NM_001382391
Type: single nucleotide variant
Location: chr8:67095461 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34
Residue 218: the 'disordered' region

Full CSPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CSPP1-related disorder

Similar variants

CSPP1 p.Arg218Gln Uncertain significance ★ same residue
CSPP1 c.1497-2A>C Likely pathogenic ★★ same condition
CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.923+1G>C Pathogenic ★★ same condition
CSPP1 c.-69C>T Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Arg15Ter Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Arg396Gln Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Arg779Ter Pathogenic/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/cspp1-p-arg218ter (accessed [today's date]).

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