Is CHD8 p.Phe1955fs (c.5856_5863dup) pathogenic?

CHD8 p.Phe1955fs (c.58565863dup) is classified Pathogenic in CHD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). Absent from gnomAD; Associated with neurodevelopmental disorder.

What condition is associated with CHD8 p.Phe1955fs (c.5856_5863dup)?

CHD8 p.Phe1955fs (c.5856_5863dup) is associated with neurodevelopmental disorder (ClinVar).

How common is CHD8 p.Phe1955fs (c.5856_5863dup) in the general population?

CHD8 p.Phe1955fs (c.5856_5863dup) is absent from gnomAD (gnomAD).

CHD8 p.Phe1955fs

c.5856_5863dup · rs2501857420 · VCV2627837

Pathogenic Single submitter

Classification

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

neurodevelopmental disorder

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 32 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, 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.Phe1955fs
Coding: c.5856_5863dup
MANE Select: NM_001170629
dbSNP: rs2501857420
Type: Duplication
Location: chr14:21393931 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 1955: the 'interaction with fam124b' region

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD8 p.Asn2371fs Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD8 p.Arg1242Ter Pathogenic ★★ same condition
CHD8 p.Lys2287del Uncertain significance ★★ same condition
CHD8 c.2364+1G>C Likely pathogenic ★ same condition
CHD8 c.2487-1G>C Likely pathogenic ★ same condition
CHD8 p.Ile1108fs Pathogenic ★★ same type
CHD8 p.Tyr1645Ter Pathogenic/Likely pathogenic ★★ same type
CHD8 c.2487-28_2487-27dup Benign/Likely benign ★★ 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-phe1955fs (accessed [today's date]).

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