Is CHD8 p.Pro368fs (c.1100dup) pathogenic?

CHD8 p.Pro368fs (c.1100dup) is classified Likely pathogenic in CHD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-23). No gnomAD frequency available for this variant; Associated with intellectual developmental disorder with autism and macrocephaly.

What condition is associated with CHD8 p.Pro368fs (c.1100dup)?

CHD8 p.Pro368fs (c.1100dup) is associated with intellectual developmental disorder with autism and macrocephaly (ClinVar).

How common is CHD8 p.Pro368fs (c.1100dup) in the general population?

CHD8 p.Pro368fs (c.1100dup) is no gnomAD frequency available for this variant (gnomAD).

How is CHD8 overgrowth syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CHD8 p.Pro368fs

c.1100dup · rs2502006766 · VCV2439079

Likely pathogenic Single submitter

Classification

Likely 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 developmental disorder with autism and macrocephaly

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 3 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.73	GERP -3.3, phastCons 0.025

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: CHD8
Protein: p.Pro368fs
Coding: c.1100dup
MANE Select: NM_001170629
dbSNP: rs2502006766
Type: Duplication
Location: chr14:21429078 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 368: the 'disordered' region

Full CHD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with autism and macrocephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CHD8 overgrowth syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

CHD8 p.Tyr1645Ter Pathogenic/Likely pathogenic ★★ same condition
CHD8 p.Asp1278fs Likely pathogenic ★ same condition
CHD8 p.Cys1483fs Likely pathogenic ★ same condition
CHD8 p.Glu1035fs Likely pathogenic ★ same condition
CHD8 p.Ser1526fs Likely pathogenic ★ same condition
CHD8 p.Tyr585fs Likely pathogenic ★ same condition
CHD8 c.7182+1dup Uncertain significance ★ same condition
CHD8 p.Asn2371fs Conflicting classifications of pathogenicity ★ ⚠ 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/chd8-p-pro368fs (accessed [today's date]).

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