Is CPLANE1 p.Ala2472Pro (c.7414G>C) pathogenic?

CPLANE1 p.Ala2472Pro (c.7414G>C) is classified Uncertain significance in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-22). AlphaMissense: likely pathogenic (0.6657); Absent from gnomAD v4.1.

How common is CPLANE1 p.Ala2472Pro (c.7414G>C) in the general population?

CPLANE1 p.Ala2472Pro (c.7414G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPLANE1 p.Ala2472Pro (c.7414G>C)?

AlphaMissense predicts likely pathogenic (score 0.6657) — an in-silico prediction, not a clinical call.

CPLANE1 p.Ala2472Pro

c.7414G>C · VCV3635367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6657 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6657	likely pathogenic · top 10% in CPLANE1
REVEL	0.066	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -3.4, phastCons 0.003
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	15.64	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPLANE1
Protein: p.Ala2472Pro
Coding: c.7414G>C
MANE Select: NM_001384732
Type: single nucleotide variant
Location: chr5:37165658 (GRCh38)
Gene constraint: LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2472: a UniProt-annotated variant site (in ofd6; likely pathogenic); the 'disordered' region

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

Similar variants

CPLANE1 p.Ala2472Thr Benign/Likely benign ★★ same residue
CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same type
CPLANE1 c.2291+1G>A Likely pathogenic ★★ same type
CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same type
CPLANE1 c.2292-1G>A Likely pathogenic ★★ same type
CPLANE1 c.2500+1G>A Likely pathogenic ★★ same type
CPLANE1 c.2920+1G>A Likely pathogenic ★★ same type
CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same type

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-ala2472pro (accessed [today's date]).

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