Is CHD8 p.Asp962Val (c.2885A>T) pathogenic?

CHD8 p.Asp962Val (c.2885A>T) is classified Uncertain significance in CHD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely pathogenic (0.9874); Absent from gnomAD v4.1.

How common is CHD8 p.Asp962Val (c.2885A>T) in the general population?

CHD8 p.Asp962Val (c.2885A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD8 p.Asp962Val (c.2885A>T)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

CHD8 p.Asp962Val

c.2885A>T · rs2139478403 · VCV1312977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 9,080 bp · p 5.6e-32 · regional, not allelic
Overall
CADD	25.4	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.Asp962Val
Coding: c.2885A>T
MANE Select: NM_001170629
dbSNP: rs2139478403
Type: single nucleotide variant
Location: chr14:21406878 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 962: the helicase atp-binding domain

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

Similar variants

CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD8 p.Arg1188Ter Pathogenic ★★ same type
CHD8 p.Arg1242Gln Likely pathogenic ★★ same type
CHD8 p.Arg1242Ter Pathogenic ★★ same type
CHD8 p.Arg1245Ter Pathogenic ★★ same type
CHD8 p.Arg1337Ter Pathogenic ★★ same type
CHD8 p.Arg1402Ter Pathogenic/Likely pathogenic ★★ same type
CHD8 p.Arg1460Ter Pathogenic ★★ same type

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-asp962val (accessed [today's date]).

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