Is CHD2 p.Asn4Ser (c.11A>G) pathogenic?

CHD2 p.Asn4Ser (c.11A>G) is classified Uncertain significance in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-17). AlphaMissense: likely benign (0.0793); Very rare (popmax 0.00501%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Asn4Ser (c.11A>G)?

CHD2 p.Asn4Ser (c.11A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Asn4Ser (c.11A>G) in the general population?

CHD2 p.Asn4Ser (c.11A>G) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about CHD2 p.Asn4Ser (c.11A>G)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

CHD2 p.Asn4Ser

c.11A>G · rs2052524504 · VCV1045197

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 23 kb · p 0.19 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00501% Admixed American · 3/59,854 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.00025% 4/1,597,062 alleles · very rare exomes 2/1,444,952 · genomes 2/152,110 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,951
European (non-Finnish)	8.58e-05%	1,165,308

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.Asn4Ser
Coding: c.11A>G
MANE Select: NM_001271
dbSNP: rs2052524504
Type: single nucleotide variant
Location: chr15:92901248 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 4: the 'disordered' region

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.Asn4Lys Uncertain significance ★ ⚠ same residue
CHD2 p.Asn4fs Pathogenic ★ 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-asn4ser (accessed [today's date]).

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