Is CPLANE1 p.Asn2148Ser (c.6443A>G) pathogenic?

CPLANE1 p.Asn2148Ser (c.6443A>G) is classified Benign/Likely benign in CPLANE1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.087); Rare (popmax 0.74%, eas); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Asn2148Ser (c.6443A>G)?

CPLANE1 p.Asn2148Ser (c.6443A>G) is associated with orofaciodigital syndrome type 6, Joubert syndrome 17 (ClinVar).

How common is CPLANE1 p.Asn2148Ser (c.6443A>G) in the general population?

CPLANE1 p.Asn2148Ser (c.6443A>G) is rare (popmax 0.74%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Asn2148Ser (c.6443A>G)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

CPLANE1 p.Asn2148Ser

c.6443A>G · rs150999024 · VCV353443

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.74%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

orofaciodigital syndrome type 6

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.002	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -2
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	0.097	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.74% East Asian · 332/44,892 alleles

Filtering AF 0.674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.648%

Overall 0.0229% 369/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.74%	135
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.0121%	8,279
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000254%	393,331

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.Asn2148Ser
Coding: c.6443A>G
MANE Select: NM_001384732
dbSNP: rs150999024
Type: single nucleotide variant
Location: chr5:37170060 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2148: the 'disordered' region

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 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
CPLANE1 c.677+1G>C 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-asn2148ser (accessed [today's date]).

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