Is CHN1 p.Asp456= (c.1368C>T) pathogenic?

CHN1 p.Asp456= (c.1368C>T) is classified Benign in CHN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.894%, sas).

How common is CHN1 p.Asp456= (c.1368C>T) in the general population?

CHN1 p.Asp456= (c.1368C>T) is rare (popmax 0.894%, sas) (gnomAD).

CHN1 p.Asp456=

c.1368C>T · rs559753925 · VCV788086

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.894%, sas)

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 4.6	GERP -1.1, phastCons 1
Overall
CADD	8.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.894% South Asian · 743/83,150 alleles

Filtering AF 0.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.819%

Overall 0.0499% 785/1,572,874 alleles · rare exomes 733/1,420,648 · genomes 52/152,226 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.894%	112
Middle Eastern	0.0682%	1,466
Remaining individualsnot grpmax-eligible	0.051%	1,963
African / African-American	0.00137%	73,080
European (non-Finnish)	0.000516%	193,665

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: CHN1
Protein: p.Asp456=
Coding: c.1368C>T
MANE Select: NM_001822
dbSNP: rs559753925
Type: single nucleotide variant
Location: chr2:174800128 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.41 · 2 PDB
Residue 456: the rho-gap domain; an α-helix

Full CHN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHN1 p.Asp456His Uncertain significance ★ ⚠ same residue
CHN1 c.-160C>G Uncertain significance ★★ same type
CHN1 c.-74C>T Uncertain significance ★★ same type
CHN1 p.Ala27Gly Uncertain significance ★★ ⚠ same type
CHN1 p.Asp440Gly Uncertain significance ★★ ⚠ same type
CHN1 p.Lys260Asn Uncertain significance ★★ ⚠ same type
CHN1 p.Thr167Ile Uncertain significance ★★ ⚠ same type
CHN1 p.Val65Met 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/chn1-p-asp456 (accessed [today's date]).

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