Is CHD2 p.Arg1152Trp (c.3454C>T) pathogenic?

CHD2 p.Arg1152Trp (c.3454C>T) is classified Pathogenic/Likely pathogenic in CHD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-06). AlphaMissense: likely pathogenic (0.8809); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Arg1152Trp (c.3454C>T)?

CHD2 p.Arg1152Trp (c.3454C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Arg1152Trp (c.3454C>T) in the general population?

CHD2 p.Arg1152Trp (c.3454C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Arg1152Trp (c.3454C>T)?

AlphaMissense predicts likely pathogenic (score 0.8809) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1152Trp

c.3454C>T · rs1596443241 · VCV812173

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8809 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,122)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8809	likely pathogenic ✓ concordant with ClinVar
REVEL	0.746	pathogenic-leaning
SaProt	LLR -13.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 7,276 bp · p 4.1e-09 · regional, not allelic
Overall
CADD	27.1	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

No allele count reported in gnomAD v4.1 (AN 1,606,122). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD2
Protein: p.Arg1152Trp
Coding: c.3454C>T
MANE Select: NM_001271
dbSNP: rs1596443241
Type: single nucleotide variant
Location: chr15:92991516 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1152: 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.Arg1152Gln Pathogenic ★ ⚠ same residue
CHD2 p.Arg1152Gly Likely 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-arg1152trp (accessed [today's date]).

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