Is CHN2 p.Ala387= (c.1161C>T) pathogenic?

CHN2 p.Ala387= (c.1161C>T) is classified Likely benign in CHN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-28). Ultra-rare (popmax 0.0165%, sas); Associated with CHN2-related disorder.

What condition is associated with CHN2 p.Ala387= (c.1161C>T)?

CHN2 p.Ala387= (c.1161C>T) is associated with CHN2-related disorder (ClinVar).

How common is CHN2 p.Ala387= (c.1161C>T) in the general population?

CHN2 p.Ala387= (c.1161C>T) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

CHN2 p.Ala387=

c.1161C>T · rs367881188 · VCV3042613

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

CHN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.155	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.442	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,070 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00601% 97/1,613,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
Middle Eastern	0.0164%	6,084
East Asian	0.00891%	11,222
European (non-Finnish)	0.0061%	16,388
Admixed American	0.00333%	30,000
African / African-American	0.00267%	37,466
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Ala387=
Coding: c.1161C>T
MANE Select: NM_004067
dbSNP: rs367881188
Type: single nucleotide variant
Location: chr7:29509332 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.06 · 1 PDB
Residue 387: the rho-gap domain; an α-helix

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-ala387 (accessed [today's date]).

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