Is CHN2 p.Ala335= (c.1005C>T) pathogenic?

CHN2 p.Ala335= (c.1005C>T) is classified Likely benign in CHN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-26). Rare (popmax 0.277%, afr); Associated with CHN2-related disorder.

What condition is associated with CHN2 p.Ala335= (c.1005C>T)?

CHN2 p.Ala335= (c.1005C>T) is associated with CHN2-related disorder (ClinVar).

How common is CHN2 p.Ala335= (c.1005C>T) in the general population?

CHN2 p.Ala335= (c.1005C>T) is rare (popmax 0.277%, afr) (gnomAD).

CHN2 p.Ala335=

c.1005C>T · rs148176559 · VCV3048142

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.277%, afr)

Conditions

CHN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.111	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.5	GERP -3.2
Overall
CADD	5.993	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.277% African / African-American · 206/74,496 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.234%

Overall 0.0202% 324/1,607,694 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.277%	362
Admixed American	0.0902%	1,108
Remaining individualsnot grpmax-eligible	0.0337%	2,965
Middle Eastern	0.0166%	6,028
East Asian	0.0112%	8,930
South Asian	0.00448%	22,319
European (non-Finnish)	0.00289%	34,650

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.Ala335=
Coding: c.1005C>T
MANE Select: NM_004067
dbSNP: rs148176559
Type: single nucleotide variant
Location: chr7:29507241 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 335: 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-ala335 (accessed [today's date]).

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