Is CPLANE1 p.Ala889Val (c.2666C>T) pathogenic?

CPLANE1 p.Ala889Val (c.2666C>T) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-18). AlphaMissense: likely pathogenic (0.7052); Very rare (popmax 7.21e-05%); Associated with orofaciodigital syndrome type 6.

What condition is associated with CPLANE1 p.Ala889Val (c.2666C>T)?

CPLANE1 p.Ala889Val (c.2666C>T) is associated with orofaciodigital syndrome type 6 (ClinVar).

How common is CPLANE1 p.Ala889Val (c.2666C>T) in the general population?

CPLANE1 p.Ala889Val (c.2666C>T) is very rare (popmax 7.21e-05%) (gnomAD).

What do computational predictors say about CPLANE1 p.Ala889Val (c.2666C>T)?

AlphaMissense predicts likely pathogenic (score 0.7052) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ala889Val

c.2666C>T · rs2150361119 · VCV1332738

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7052 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.21e-05%)

Conditions

orofaciodigital syndrome type 6

Computational evidence

Protein change
AlphaMissense	0.7052	likely pathogenic · top 9% in CPLANE1
REVEL	0.429	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	26.6	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 7.21e-05%

Overall 7.21e-05% 1/1,386,830 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.Ala889Val
Coding: c.2666C>T
MANE Select: NM_001384732
dbSNP: rs2150361119
Type: single nucleotide variant
Location: chr5:37221404 (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

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-ala889val (accessed [today's date]).

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