Is CNP p.Asn377Ser (c.1130A>G) pathogenic?

CNP p.Asn377Ser (c.1130A>G) is classified Likely benign in CNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0623); Very rare (popmax 0.00534%, afr).

How common is CNP p.Asn377Ser (c.1130A>G) in the general population?

CNP p.Asn377Ser (c.1130A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CNP p.Asn377Ser (c.1130A>G)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

CNP p.Asn377Ser

c.1130A>G · VCV4654989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -4.69	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 -0.33	GERP -3.6
Regional constraint	o/e 1.00	unconstrained · MANE · 5,251 bp · p 0.97 · regional, not allelic
Overall
CADD	5.598	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 0.00534% African / African-American · 4/74,922 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00105% 17/1,612,732 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,730
East Asian	0.00223%	44,852
South Asian	0.0022%	45,425
Admixed American	0.00167%	59,856
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	0.000678%	147,434

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.Asn377Ser
Coding: c.1130A>G
MANE Select: NM_033133
Type: single nucleotide variant
Location: chr17:41973788 (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-asn377ser (accessed [today's date]).

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