Is CHD8 p.Gln331Arg (c.992A>G) pathogenic?

CHD8 p.Gln331Arg (c.992A>G) is classified Conflicting classifications of pathogenicity in CHD8 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-04-24). AlphaMissense: ambiguous (0.4424); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD8 p.Gln331Arg (c.992A>G)?

CHD8 p.Gln331Arg (c.992A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD8 p.Gln331Arg (c.992A>G) in the general population?

CHD8 p.Gln331Arg (c.992A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD8 p.Gln331Arg (c.992A>G)?

AlphaMissense predicts ambiguous (score 0.4424) — an in-silico prediction, not a clinical call.

CHD8 p.Gln331Arg

c.992A>G · rs1566444686 · VCV589689

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4424 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4424	ambiguous
REVEL	0.386	indeterminate
SaProt	LLR -8.23	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,193 bp · p 0.15 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD8
Protein: p.Gln331Arg
Coding: c.992A>G
MANE Select: NM_001170629
dbSNP: rs1566444686
Type: single nucleotide variant
Location: chr14:21429187 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD8 p.Gln331Ter Pathogenic ★ same residue
CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD8 p.Arg1462Ter Pathogenic ★★ same condition
CHD8 p.Arg1582Ter Pathogenic/Likely pathogenic ★★ same condition
CHD8 p.Arg2217Ter Pathogenic ★★ same condition
CHD8 p.Arg243Ter Pathogenic ★★ same condition
CHD8 c.4921+4C>T Uncertain significance ★★ same condition
CHD8 c.-1G>A Uncertain significance ★★ 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-gln331arg (accessed [today's date]).

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