Is CSPP1 p.Arg230Ile (c.689G>T) pathogenic?

CSPP1 p.Arg230Ile (c.689G>T) is classified Uncertain significance in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Arg230Ile (c.689G>T)?

CSPP1 p.Arg230Ile (c.689G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSPP1 p.Arg230Ile (c.689G>T) in the general population?

CSPP1 p.Arg230Ile (c.689G>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

CSPP1 p.Arg230Ile

c.689G>T · VCV4007682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.161	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,852 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000434% 7/1,613,306 alleles · ultra-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: CSPP1
Protein: p.Arg230Ile
Coding: c.689G>T
MANE Select: NM_001382391
Type: single nucleotide variant
Location: chr8:67095498 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34
Residue 230: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSPP1 c.-57C>G Uncertain significance ★★ same condition
CSPP1 p.Ala38Val Uncertain significance ★★ same condition
CSPP1 p.Ala523Glu Uncertain significance ★★ same condition
CSPP1 p.Ala653Val Uncertain significance ★★ same condition
CSPP1 p.Arg258Lys Uncertain significance ★★ same condition
CSPP1 p.Arg291Ser Uncertain significance ★★ same condition
CSPP1 p.Arg314Gln Uncertain significance ★★ same condition
CSPP1 p.Arg453Ser 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/cspp1-p-arg230ile (accessed [today's date]).

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