Is CNP p.Lys20Arg (c.59A>G) pathogenic?

CNP p.Lys20Arg (c.59A>G) is classified Pathogenic in CNP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-14). AlphaMissense: likely benign (0.1268); Very rare (popmax 0.00223%, eas); Associated with myopia 2, autosomal dominant.

What condition is associated with CNP p.Lys20Arg (c.59A>G)?

CNP p.Lys20Arg (c.59A>G) is associated with myopia 2, autosomal dominant (ClinVar).

How common is CNP p.Lys20Arg (c.59A>G) in the general population?

CNP p.Lys20Arg (c.59A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CNP p.Lys20Arg (c.59A>G)?

AlphaMissense predicts likely benign (score 0.1268) — an in-silico prediction, not a clinical call.

CNP p.Lys20Arg

c.59A>G · rs199923805 · VCV834077

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1268 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopia 2, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.1268	likely benign ⚠ discordant with ClinVar
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.6, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,784 bp · p 6.9e-09 · regional, not allelic
Overall
CADD	22.7	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 · 1/44,878 alleles

Overall 0.000124% 2/1,614,250 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	8.47e-05%	1,180,048

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: CNP
Protein: p.Lys20Arg
Coding: c.59A>G
MANE Select: NM_033133
dbSNP: rs199923805
Type: single nucleotide variant
Location: chr17:41968123 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.54 · 1 PDB

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

Disease context

myopia 2, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNP p.Lys20Thr Pathogenic ⚠ same residue
CNP p.Lys20Glu Uncertain significance ★ ⚠ same residue
CNP p.Lys20Met Uncertain significance ★ ⚠ same residue
CNP p.Val339Ile Uncertain significance ★ ⚠ same condition
CNP c.-67C>T Pathogenic same condition
CNP p.Gly345Asp Pathogenic same condition
CNP p.Arg353Trp Uncertain significance ★★ ⚠ same type
CNP p.Gly365= Benign ★★ 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/cnp-p-lys20arg (accessed [today's date]).

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