Is CHD8 p.Arg574fs (c.1720del) pathogenic?

CHD8 p.Arg574fs (c.1720del) is classified Likely pathogenic in CHD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-16). No gnomAD frequency available for this variant; Associated with CHD8-associated Neurodevelopmental syndrome.

What condition is associated with CHD8 p.Arg574fs (c.1720del)?

CHD8 p.Arg574fs (c.1720del) is associated with CHD8-associated Neurodevelopmental syndrome (ClinVar).

How common is CHD8 p.Arg574fs (c.1720del) in the general population?

CHD8 p.Arg574fs (c.1720del) is no gnomAD frequency available for this variant (gnomAD).

CHD8 p.Arg574fs

c.1720del · rs2139499999 · VCV1696513

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

CHD8-associated Neurodevelopmental syndrome

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 6 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, 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: CHD8
Protein: p.Arg574fs
Coding: c.1720del
MANE Select: NM_001170629
dbSNP: rs2139499999
Type: Deletion
Location: chr14:21415904 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 574: the 'disordered' region

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

Disease context

CHD8-associated Neurodevelopmental syndrome

Similar variants

CHD8 p.Glu509fs Likely pathogenic ★ same condition
CHD8 p.Gly2435fs Likely pathogenic ★ same condition
CHD8 p.His2498fs Likely pathogenic ★ same condition
CHD8 p.Phe711fs Pathogenic ★ same condition
CHD8 p.Ser2057fs Likely pathogenic ★ same condition
CHD8 p.Ser491fs Likely pathogenic ★ same condition
CHD8 p.Asn13fs Uncertain significance same condition
CHD8 p.Arg1472Ter 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/chd8-p-arg574fs (accessed [today's date]).

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