Is CHD8 p.Lys528fs (c.1582_1583del) pathogenic?

CHD8 p.Lys528fs (c.15821583del) is classified Pathogenic in CHD8 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with autism spectrum disorder.

What condition is associated with CHD8 p.Lys528fs (c.1582_1583del)?

CHD8 p.Lys528fs (c.1582_1583del) is associated with autism spectrum disorder (ClinVar).

How common is CHD8 p.Lys528fs (c.1582_1583del) in the general population?

CHD8 p.Lys528fs (c.1582_1583del) is absent from gnomAD (gnomAD).

CHD8 p.Lys528fs

c.1582_1583del · rs2502001713 · VCV2430092

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

autism spectrum 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 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -3.6, phastCons 1
Region caveats
Repeat context	tandem	GTCCCATCCCAATAGCAAGGAGTACTCACTTGAGCTTACTCTTGCACGTCCCATCACAGTAGCAAGGAGCACTCACTTGAGCTTGCTCTTGCCCTTTGTTTTGGAGGTACCAGATGTTTGCTCTGCCCTCAAAT simple repeat · ambiguous alignment · confidence, not pathogenicity

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.Lys528fs
Coding: c.1582_1583del
MANE Select: NM_001170629
dbSNP: rs2502001713
Type: Deletion
Location: chr14:21427887 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 528: the 'disordered' region

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

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD8 p.His782fs Pathogenic ★ same condition
CHD8 p.Arg1460Ter Pathogenic ★★ same condition
CHD8 c.3519-2A>G Pathogenic ★ same condition
CHD8 p.Arg952Ter Pathogenic ★ same condition
CHD8 p.Gln1171Ter Pathogenic ★ same condition
CHD8 p.Gly1103Val Likely pathogenic ★ same condition
CHD8 p.Leu980fs Pathogenic ★ same condition
CHD8 p.Arg2420Cys 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-lys528fs (accessed [today's date]).

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