Is CSPP1 p.Arg272Trp (c.814C>T) pathogenic?

CSPP1 p.Arg272Trp (c.814C>T) is classified Conflicting classifications of pathogenicity in CSPP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-07). Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with CSPP1 p.Arg272Trp (c.814C>T)?

CSPP1 p.Arg272Trp (c.814C>T) is associated with Inborn genetic diseases, Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg272Trp (c.814C>T) in the general population?

CSPP1 p.Arg272Trp (c.814C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

CSPP1 p.Arg272Trp

c.814C>T · rs756423026 · VCV423591

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.146	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.7, phastCons 0.58
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,054 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00645% 104/1,612,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,027
Admixed American	0.02%	4,998
Remaining individualsnot grpmax-eligible	0.0112%	8,925
South Asian	0.00989%	10,116
East Asian	0.00892%	11,214
African / African-American	0.00667%	14,983
Finnishnot grpmax-eligible	0.00626%	15,974
European (non-Finnish)	0.00509%	19,655
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596

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.Arg272Trp
Coding: c.814C>T
MANE Select: NM_001382391
dbSNP: rs756423026
Type: single nucleotide variant
Location: chr8:67095623 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34

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

Also linked: Joubert syndrome 21

Similar variants

CSPP1 p.Arg272Gln Likely benign ★★ same residue
CSPP1 p.Arg272= Likely benign ★ same residue
CSPP1 c.1022+1G>T Likely pathogenic ★★ same condition
CSPP1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.1497-2A>C Likely pathogenic ★★ same condition
CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same condition
CSPP1 c.2968+1G>A Pathogenic ★★ same condition
CSPP1 c.2968+1G>T 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-arg272trp (accessed [today's date]).

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