Is CHD8 p.Arg952Ter (c.2854C>T) pathogenic?

CHD8 p.Arg952Ter (c.2854C>T) is classified Pathogenic in CHD8 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-02). Very rare (popmax 8.48e-05%, nfe); Associated with autism spectrum disorder.

What condition is associated with CHD8 p.Arg952Ter (c.2854C>T)?

CHD8 p.Arg952Ter (c.2854C>T) is associated with autism spectrum disorder (ClinVar).

How common is CHD8 p.Arg952Ter (c.2854C>T) in the general population?

CHD8 p.Arg952Ter (c.2854C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CHD8 p.Arg952Ter

c.2854C>T · rs1131691548 · VCV429724

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

autism spectrum disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 38
REVEL	0.525	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,732 alleles

Overall 6.84e-05% 1/1,461,288 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHD8
Protein: p.Arg952Ter
Coding: c.2854C>T
MANE Select: NM_001170629
dbSNP: rs1131691548
Type: single nucleotide variant
Location: chr14:21406909 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 952: the helicase atp-binding domain

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.Arg952Gln Likely pathogenic ★ same residue
CHD8 p.Arg952Leu Likely pathogenic ★ same residue
CHD8 p.Arg1460Ter Pathogenic ★★ same condition
CHD8 c.3519-2A>G Pathogenic ★ same condition
CHD8 p.Gln1171Ter Pathogenic ★ same condition
CHD8 p.Gly1103Val Likely pathogenic ★ same condition
CHD8 p.Arg2420Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD8 c.2365-10T>G Likely benign ★ 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-arg952ter (accessed [today's date]).

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