Is CHD2 p.Asn364Ser (c.1091A>G) pathogenic?

CHD2 p.Asn364Ser (c.1091A>G) is classified Conflicting classifications of pathogenicity in CHD2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0683); Ultra-rare (popmax 0.0497%, mid); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Asn364Ser (c.1091A>G)?

CHD2 p.Asn364Ser (c.1091A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Asn364Ser (c.1091A>G) in the general population?

CHD2 p.Asn364Ser (c.1091A>G) is ultra-rare (popmax 0.0497%, mid) (gnomAD).

What do computational predictors say about CHD2 p.Asn364Ser (c.1091A>G)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

CHD2 p.Asn364Ser

c.1091A>G · rs143043614 · VCV210708

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.43, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 9,299 bp · p 6.4e-08 · regional, not allelic
Overall
CADD	19.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% Middle Eastern · 3/6,032 alleles

Filtering AF 0.0326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0315%

Overall 0.029% 467/1,610,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0497%	2,011
European (non-Finnish)	0.0355%	2,817
Admixed American	0.0183%	5,450
Remaining individualsnot grpmax-eligible	0.0144%	6,922
African / African-American	0.0133%	7,501
East Asian	0.0112%	8,958
South Asian	0.0077%	12,984
Finnishnot grpmax-eligible	0.0047%	21,291
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,488

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.Asn364Ser
Coding: c.1091A>G
MANE Select: NM_001271
dbSNP: rs143043614
Type: single nucleotide variant
Location: chr15:92944453 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 364: 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.Asn364Ile Uncertain significance ★ ⚠ same residue
CHD2 p.Asn364Tyr 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-asn364ser (accessed [today's date]).

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