Is CPLANE1 p.Cys810Arg (c.2428T>C) pathogenic?

CPLANE1 p.Cys810Arg (c.2428T>C) is classified Uncertain significance in CPLANE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.475); Very rare (popmax 0.00238%, sas); Associated with Inborn genetic diseases.

What condition is associated with CPLANE1 p.Cys810Arg (c.2428T>C)?

CPLANE1 p.Cys810Arg (c.2428T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CPLANE1 p.Cys810Arg (c.2428T>C) in the general population?

CPLANE1 p.Cys810Arg (c.2428T>C) is very rare (popmax 0.00238%, sas) (gnomAD).

What do computational predictors say about CPLANE1 p.Cys810Arg (c.2428T>C)?

AlphaMissense predicts ambiguous (score 0.475) — an in-silico prediction, not a clinical call.

CPLANE1 p.Cys810Arg

c.2428T>C · VCV4831419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.475	ambiguous
REVEL	0.166	moderately benign-leaning
Splicing
SpliceAI	Δ0.41	acceptor loss, 12 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	24.6	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 0.00238% South Asian · 2/84,060 alleles

Filtering AF 0.000395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000148%

Overall 0.0005% 7/1,399,102 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00238%	42,030
European (non-Finnish)	0.000436%	229,360

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.Cys810Arg
Coding: c.2428T>C
MANE Select: NM_001384732
Type: single nucleotide variant
Location: chr5:37224604 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CPLANE1 p.Cys810Gly Uncertain significance ★★ ⚠ same residue
CPLANE1 p.Cys810Trp Uncertain significance ★ ⚠ same residue
CPLANE1 c.3921+6T>G Uncertain significance ★★ same condition
CPLANE1 p.Ala77Ser Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg1199Gln Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Arg3015Cys Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Asp2526Asn Uncertain significance ★★ ⚠ same condition
CPLANE1 p.Cys1280Tyr Uncertain significance ★★ ⚠ 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-cys810arg (accessed [today's date]).

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