Is CHD2 p.Arg1158Cys (c.3472C>T) pathogenic?

CHD2 p.Arg1158Cys (c.3472C>T) is classified Uncertain significance in CHD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: ambiguous (0.5338); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Arg1158Cys (c.3472C>T)?

CHD2 p.Arg1158Cys (c.3472C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Arg1158Cys (c.3472C>T) in the general population?

CHD2 p.Arg1158Cys (c.3472C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD2 p.Arg1158Cys (c.3472C>T)?

AlphaMissense predicts ambiguous (score 0.5338) — an in-silico prediction, not a clinical call.

CHD2 p.Arg1158Cys

c.3472C>T · rs2505580479 · VCV2838957

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5338	ambiguous
REVEL	0.402	indeterminate
SaProt	LLR -9.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 7,276 bp · p 4.1e-09 · regional, not allelic
Overall
CADD	28.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD2
Protein: p.Arg1158Cys
Coding: c.3472C>T
MANE Select: NM_001271
dbSNP: rs2505580479
Type: single nucleotide variant
Location: chr15:92992875 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1158: 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.Arg1158His Uncertain significance ★ ⚠ same residue
CHD2 p.Arg1158Pro Uncertain significance ★ ⚠ same residue
CHD2 p.Arg1158Leu 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

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-arg1158cys (accessed [today's date]).

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