Is CPLANE1 p.Ser437= (c.1311A>G) pathogenic?

CPLANE1 p.Ser437= (c.1311A>G) is classified Likely benign in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-15). Very rare (popmax 8.72e-05%, nfe); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Ser437= (c.1311A>G)?

CPLANE1 p.Ser437= (c.1311A>G) is associated with orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Ser437= (c.1311A>G) in the general population?

CPLANE1 p.Ser437= (c.1311A>G) is very rare (popmax 8.72e-05%, nfe) (gnomAD).

CPLANE1 p.Ser437=

c.1311A>G · rs761587080 · VCV740873

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.72e-05%, nfe)

Conditions

orofaciodigital syndrome type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -0.97
Overall
CADD	4.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.72e-05% European (non-Finnish) · 1/1,146,570 alleles

Overall 7.15e-05% 1/1,398,936 alleles · very 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: CPLANE1
Protein: p.Ser437=
Coding: c.1311A>G
MANE Select: NM_001384732
dbSNP: rs761587080
Type: single nucleotide variant
Location: chr5:37227628 (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.Ser437Leu Uncertain significance ★ ⚠ 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.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.3673-1G>C 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-ser437 (accessed [today's date]).

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