Is CPLANE1 p.Met1958fs (c.5872dup) pathogenic?

CPLANE1 p.Met1958fs (c.5872dup) is classified Pathogenic/Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). Absent from gnomAD; Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Met1958fs (c.5872dup)?

CPLANE1 p.Met1958fs (c.5872dup) is associated with orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Met1958fs (c.5872dup) in the general population?

CPLANE1 p.Met1958fs (c.5872dup) is absent from gnomAD (gnomAD).

CPLANE1 p.Met1958fs

c.5872dup · rs2547728684 · VCV2971656

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

orofaciodigital syndrome type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 30 of 53
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.69	GERP -2.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPLANE1
Protein: p.Met1958fs
Coding: c.5872dup
MANE Select: NM_001384732
dbSNP: rs2547728684
Type: Duplication
Location: chr5:37177648 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

orofaciodigital syndrome type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 17

Similar variants

CPLANE1 p.Asn1339Ter Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Asn1865fs Pathogenic ★★ same condition
CPLANE1 p.Asp1467fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Cys1277fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.His3148fs Likely pathogenic ★★ same condition
CPLANE1 p.Ile2119fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Ile980fs Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Leu1386fs 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/cplane1-p-met1958fs (accessed [today's date]).

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