Is CHD8 p.Ser45= (c.133_134delinsAG) pathogenic?

CHD8 p.Ser45= (c.133134delinsAG) is classified Uncertain significance in CHD8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). Absent from gnomAD.

How common is CHD8 p.Ser45= (c.133_134delinsAG) in the general population?

CHD8 p.Ser45= (c.133_134delinsAG) is absent from gnomAD (gnomAD).

CHD8 p.Ser45=

c.133_134delinsAG · rs2502016757 · VCV2866420

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1

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.Ser45=
Coding: c.133_134delinsAG
MANE Select: NM_001170629
dbSNP: rs2502016757
Type: Indel
Location: chr14:21431510 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 45: the 'disordered' region

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

Similar variants

CHD8 p.Ala1147fs Pathogenic ★ same type
CHD8 p.Arg956fs Likely pathogenic ★ same type
CHD8 p.Asp948fs Pathogenic ★ same type
CHD8 p.Leu980fs Pathogenic ★ same type
CHD8 p.Pro861fs Pathogenic ★ same type
CHD8 p.Ser491_Val492delinsArgGly Pathogenic ★ same type
CHD8 c.1599_1601+6delinsGAAGTGAGG Uncertain significance ★ same type
CHD8 c.2731-24_2731-7delinsCTAAGCATGAAG Uncertain significance ★ 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-ser45 (accessed [today's date]).

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