Is CHD2 p.Asn590= (c.1770C>T) pathogenic?

CHD2 p.Asn590= (c.1770C>T) is classified Likely benign in CHD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Asn590= (c.1770C>T)?

CHD2 p.Asn590= (c.1770C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Asn590= (c.1770C>T) in the general population?

CHD2 p.Asn590= (c.1770C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CHD2 p.Asn590=

c.1770C>T · rs149947056 · VCV391318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

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 -0.79	GERP -5.9, phastCons 0.016
Overall
CADD	8.664	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,044 alleles

Filtering AF 0.00461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00175% 28/1,596,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
Admixed American	0.0106%	9,407
Finnishnot grpmax-eligible	0.00945%	10,587
African / African-American	0.00543%	18,419
Remaining individualsnot grpmax-eligible	0.00324%	30,895
South Asian	0.00228%	43,863
European (non-Finnish)	0.000596%	167,687

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: CHD2
Protein: p.Asn590=
Coding: c.1770C>T
MANE Select: NM_001271
dbSNP: rs149947056
Type: single nucleotide variant
Location: chr15:92955473 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 590: the helicase atp-binding domain; a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy 94

Similar variants

CHD2 p.Asn590Ser Uncertain significance ★★ ⚠ same residue
CHD2 p.Asn590His Uncertain significance ★ ⚠ same residue
CHD2 c.1153+1G>C Pathogenic ★★ same condition
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.294+1G>T Likely pathogenic ★★ same condition
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.693-1G>A Likely pathogenic ★★ same condition
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ 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/chd2-p-asn590 (accessed [today's date]).

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