Is CPLANE1 p.Gln1345Arg (c.4034A>G) pathogenic?

CPLANE1 p.Gln1345Arg (c.4034A>G) is classified Likely pathogenic in CPLANE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). AlphaMissense: likely pathogenic (0.7429); Very rare (popmax 0.00223%, eas); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Gln1345Arg (c.4034A>G)?

CPLANE1 p.Gln1345Arg (c.4034A>G) is associated with orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Gln1345Arg (c.4034A>G) in the general population?

CPLANE1 p.Gln1345Arg (c.4034A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Gln1345Arg (c.4034A>G)?

AlphaMissense predicts likely pathogenic (score 0.7429) — an in-silico prediction, not a clinical call.

CPLANE1 p.Gln1345Arg

c.4034A>G · rs869312898 · VCV224854

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

orofaciodigital syndrome type 6

Computational evidence

Protein change
AlphaMissense	0.7429	likely pathogenic ✓ concordant with ClinVar · top 8% in CPLANE1
REVEL	0.514	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	25.1	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 0.00223% East Asian · 1/44,864 alleles

Overall 0.000124% 2/1,613,686 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,864
African / African-American	0.00133%	74,924

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.Gln1345Arg
Coding: c.4034A>G
MANE Select: NM_001384732
dbSNP: rs869312898
Type: single nucleotide variant
Location: chr5:37187460 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1345: a UniProt-annotated variant site (in ofd6)

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

Similar variants

CPLANE1 p.Gln1345Ter Pathogenic ★ 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-gln1345arg (accessed [today's date]).

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