Is CHN2 p.Asn423= (c.1269T>C) pathogenic?

CHN2 p.Asn423= (c.1269T>C) is classified Benign in CHN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-18). Common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CHN2-related disorder.

What condition is associated with CHN2 p.Asn423= (c.1269T>C)?

CHN2 p.Asn423= (c.1269T>C) is associated with CHN2-related disorder (ClinVar).

CHN2 p.Asn423=

Q: How common is CHN2 p.Asn423= (c.1269T>C) in the general population?

CHN2 p.Asn423= (c.1269T>C) is common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1269T>C · rs3750099 · VCV3060363

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CHN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP 0.75
Overall
CADD	2.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.3% African / African-American · 32,421/74,828 alleles

Filtering AF 42.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.8%

Overall 5.47% 88,259/1,613,070 alleles · common exomes 64,155/1,460,948 · genomes 24,104/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	43.3%	2
East Asian	29%	3
Admixed American	15.8%	6
South Asian	13.3%	8
Amishnot grpmax-eligible	10.1%	10
Middle Eastern	7.52%	13
Finnishnot grpmax-eligible	7.41%	13
Remaining individualsnot grpmax-eligible	7.27%	14
Ashkenazi Jewishnot grpmax-eligible	1.8%	55
European (non-Finnish)	0.927%	108

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: CHN2
Protein: p.Asn423=
Coding: c.1269T>C
MANE Select: NM_004067
dbSNP: rs3750099
Type: single nucleotide variant
Location: chr7:29512597 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 423: the rho-gap domain

Full CHN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHN2-related disorder

Similar variants

CHN2 c.291-7C>T Benign same condition
CHN2 c.50-61702A>T Benign same condition
CHN2 c.-442T>C Likely benign same condition
CHN2 c.-501-8C>T Benign same condition
CHN2 c.-511T>G Benign same condition
CHN2 c.-601C>T Likely benign same condition
CHN2 c.-646G>A Benign same condition
CHN2 c.-6G>A Likely benign 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/chn2-p-asn423 (accessed [today's date]).

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