Is CHD2 p.Lys349fs (c.1044del) pathogenic?

CHD2 p.Lys349fs (c.1044del) is classified Pathogenic in CHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). Absent from gnomAD; Associated with intellectual disability.

What condition is associated with CHD2 p.Lys349fs (c.1044del)?

CHD2 p.Lys349fs (c.1044del) is associated with intellectual disability (ClinVar).

How common is CHD2 p.Lys349fs (c.1044del) in the general population?

CHD2 p.Lys349fs (c.1044del) is absent from gnomAD (gnomAD).

CHD2 p.Lys349fs

c.1044del · rs2053407118 · VCV981452

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability

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 9 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.3	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Lys349fs
Coding: c.1044del
MANE Select: NM_001271
dbSNP: rs2053407118
Type: Deletion
Location: chr15:92943060 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 349: the chromo 1 domain; 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

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD2 p.Lys1391fs Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD2 p.Lys349Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD2 p.Gly1450fs Pathogenic same condition
CHD2 p.Arg1546Ter Pathogenic ★★ same condition
CHD2 p.Arg699Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg846Ter Pathogenic ★★ same condition
CHD2 p.Gln1523Ter Pathogenic ★★ same condition
CHD2 p.Glu1006_Asn1007insTer 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-lys349fs (accessed [today's date]).

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