Is CHD2 p.Arg111fs (c.331_333delinsA) pathogenic?

CHD2 p.Arg111fs (c.331333delinsA) is classified Likely pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-25). Associated with CHD2-related disorder.

What condition is associated with CHD2 p.Arg111fs (c.331_333delinsA)?

CHD2 p.Arg111fs (c.331_333delinsA) is associated with CHD2-related disorder (ClinVar).

CHD2 p.Arg111fs

c.331_333delinsA · VCV4926665

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

CHD2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.17	GERP -0.44, phastCons 0.93

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CHD2
Protein: p.Arg111fs
Coding: c.331_333delinsA
MANE Select: NM_001271
Type: Indel
Location: chr15:92927280 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 111: the 'disordered' region

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

Disease context

CHD2-related disorder

Similar variants

CHD2 p.Arg111= Likely benign ★ same residue
CHD2 p.Arg1313Ter Pathogenic ★★ same condition
CHD2 p.Arg1546Ter Pathogenic ★★ same condition
CHD2 p.Arg224Ter Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg466Ter Pathogenic ★★ same condition
CHD2 p.Gln1641Ter Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Tyr1700Ter Pathogenic ★★ same condition
CHD2 c.2352+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-arg111fs (accessed [today's date]).

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