Is CNP p.Val339Ile (c.1015G>A) pathogenic?

CNP p.Val339Ile (c.1015G>A) is classified Uncertain significance in CNP (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-23). AlphaMissense: likely benign (0.0866); Ultra-rare (popmax 0.0223%, eas); Associated with myopia 2, autosomal dominant.

What condition is associated with CNP p.Val339Ile (c.1015G>A)?

CNP p.Val339Ile (c.1015G>A) is associated with myopia 2, autosomal dominant (ClinVar).

How common is CNP p.Val339Ile (c.1015G>A) in the general population?

CNP p.Val339Ile (c.1015G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about CNP p.Val339Ile (c.1015G>A)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

CNP p.Val339Ile

c.1015G>A · rs782532165 · VCV834078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopia 2, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -7.50	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 3.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,251 bp · p 0.97 · regional, not allelic
Overall
CADD	18.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,886 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00118% 19/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
South Asian	0.0011%	91,062
European (non-Finnish)	0.000678%	147,501

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.Val339Ile
Coding: c.1015G>A
MANE Select: NM_033133
dbSNP: rs782532165
Type: single nucleotide variant
Location: chr17:41973673 (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 c.-67C>T Pathogenic same condition
CNP p.Gly345Asp Pathogenic same condition
CNP p.Lys20Arg Pathogenic ⚠ same condition
CNP p.Lys20Thr Pathogenic ⚠ same condition
CNP p.Arg353Trp Uncertain significance ★★ ⚠ same type
CNP p.Gly365= Benign ★★ same type
CNP p.Ala218Val Uncertain significance ★ ⚠ same type
CNP p.Ala269Val Uncertain significance ★ ⚠ 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-val339ile (accessed [today's date]).

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