Is CPLANE1 p.Lys693Arg (c.2078A>G) pathogenic?

CPLANE1 p.Lys693Arg (c.2078A>G) is classified Conflicting classifications of pathogenicity in CPLANE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0617); Ultra-rare (popmax 0.0563%, eas); Associated with CPLANE1-related disorder.

What condition is associated with CPLANE1 p.Lys693Arg (c.2078A>G)?

CPLANE1 p.Lys693Arg (c.2078A>G) is associated with CPLANE1-related disorder (ClinVar).

How common is CPLANE1 p.Lys693Arg (c.2078A>G) in the general population?

CPLANE1 p.Lys693Arg (c.2078A>G) is ultra-rare (popmax 0.0563%, eas) (gnomAD).

What do computational predictors say about CPLANE1 p.Lys693Arg (c.2078A>G)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

CPLANE1 p.Lys693Arg

c.2078A>G · rs181812684 · VCV1961393

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0563%, eas)

Conditions

CPLANE1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.41	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 139 kb · p 2.3e-06 · regional, not allelic
Overall
CADD	0.18	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 0.0563% East Asian · 23/40,834 alleles

Filtering AF 0.0384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0326%

Overall 0.00497% 77/1,548,312 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0563%	1,775
Middle Eastern	0.0167%	5,972
South Asian	0.00961%	10,403
African / African-American	0.00549%	18,229
European (non-Finnish)	0.00349%	28,646
Remaining individualsnot grpmax-eligible	0.00167%	59,930

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.Lys693Arg
Coding: c.2078A>G
MANE Select: NM_001384732
dbSNP: rs181812684
Type: single nucleotide variant
Location: chr5:37226517 (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

CPLANE1-related disorder

Similar variants

CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 c.2920+1G>A Likely pathogenic ★★ same condition
CPLANE1 c.7400+1G>A Pathogenic ★★ same condition
CPLANE1 p.Ala1200Val Pathogenic ★★ same condition
CPLANE1 p.Arg1226Ter Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Arg2493Ter Pathogenic ★★ same condition
CPLANE1 p.Arg2714Ter Pathogenic/Likely pathogenic ★★ same condition
CPLANE1 p.Arg2958Ter 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-lys693arg (accessed [today's date]).

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