Is CNP p.Arg360Gln (c.1079G>A) pathogenic?

CNP p.Arg360Gln (c.1079G>A) is classified Uncertain significance in CNP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.0799); Ultra-rare (popmax 0.0462%, sas).

How common is CNP p.Arg360Gln (c.1079G>A) in the general population?

CNP p.Arg360Gln (c.1079G>A) is ultra-rare (popmax 0.0462%, sas) (gnomAD).

What do computational predictors say about CNP p.Arg360Gln (c.1079G>A)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

CNP p.Arg360Gln

c.1079G>A · rs376149897 · VCV2272907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.22	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 1.4	GERP -0.35, phastCons 0.8
Regional constraint	o/e 1.00	unconstrained · MANE · 5,251 bp · p 0.97 · regional, not allelic
Overall
CADD	16.58	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 0.0462% South Asian · 42/90,858 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00807% 130/1,611,726 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0462%	2,163
Remaining individualsnot grpmax-eligible	0.00962%	10,399
East Asian	0.00669%	14,941
Admixed American	0.00669%	14,952
European (non-Finnish)	0.00611%	16,370
African / African-American	0.004%	25,006

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.Arg360Gln
Coding: c.1079G>A
MANE Select: NM_033133
dbSNP: rs376149897
Type: single nucleotide variant
Location: chr17:41973737 (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

Similar variants

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
CNP p.Ala281Val Uncertain significance ★ ⚠ same type
CNP p.Ala92Thr Uncertain significance ★ ⚠ same type
CNP p.Arg114Gln Uncertain significance ★ ⚠ same type
CNP p.Arg128Gln 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-arg360gln (accessed [today's date]).

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