Is CPLANE1 p.Arg2958Ter (c.8872C>T) pathogenic?

CPLANE1 p.Arg2958Ter (c.8872C>T) is classified Pathogenic in CPLANE1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-11). Very rare (popmax 0.00432%, nfe); Associated with C5ORF42 & CPLANE1-related disorders.

What condition is associated with CPLANE1 p.Arg2958Ter (c.8872C>T)?

CPLANE1 p.Arg2958Ter (c.8872C>T) is associated with C5ORF42 & CPLANE1-related disorders, orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Arg2958Ter (c.8872C>T) in the general population?

CPLANE1 p.Arg2958Ter (c.8872C>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

CPLANE1 p.Arg2958Ter

c.8872C>T · rs141507441 · VCV217571

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Conditions

C5ORF42 & CPLANE1-related disorders

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 47 of 53
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1, phastCons 0.98
Overall
CADD	38.0	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 0.00432% European (non-Finnish) · 51/1,179,812 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00341% 55/1,613,420 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,134
Admixed American	0.00334%	29,962
East Asian	0.00223%	44,844
South Asian	0.0011%	91,060

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: CPLANE1
Protein: p.Arg2958Ter
Coding: c.8872C>T
MANE Select: NM_001384732
dbSNP: rs141507441
Type: single nucleotide variant
Location: chr5:37125330 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2958: a UniProt-annotated variant site (in ofd6; likely pathogenic)

Full CPLANE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

C5ORF42 & CPLANE1-related disorders

Also linked: orofaciodigital syndrome type 6 Joubert syndrome 17

Similar variants

CPLANE1 p.Arg2958Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CPLANE1 p.Arg2958= Likely benign ★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.2920+1G>A 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/cplane1-p-arg2958ter (accessed [today's date]).

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