Is CHD8 p.Phe1687fs (c.5061del) pathogenic?

CHD8 p.Phe1687fs (c.5061del) is classified Pathogenic in CHD8 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with Macrocephaly.

What condition is associated with CHD8 p.Phe1687fs (c.5061del)?

CHD8 p.Phe1687fs (c.5061del) is associated with Macrocephaly (ClinVar).

How common is CHD8 p.Phe1687fs (c.5061del) in the general population?

CHD8 p.Phe1687fs (c.5061del) is absent from gnomAD (gnomAD).

CHD8 p.Phe1687fs

c.5061del · rs2139452398 · VCV1172605

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

Macrocephaly

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 28 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, 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.Phe1687fs
Coding: c.5061del
MANE Select: NM_001170629
dbSNP: rs2139452398
Type: Deletion
Location: chr14:21395883 (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

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

Similar variants

CHD8 p.Arg578Cys Likely pathogenic ★★ same condition
CHD8 p.Arg2150fs Pathogenic/Likely pathogenic ★★ same type
CHD8 p.Gly1602fs Pathogenic ★★ same type
CHD8 p.Lys1537_Val1538insTer Likely pathogenic ★★ same type
CHD8 c.2487-19del Likely benign ★★ same type
CHD8 c.4174-9_4174-1del Pathogenic ★ same type
CHD8 c.4727+1del Likely pathogenic ★ same type
CHD8 c.4729del 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-phe1687fs (accessed [today's date]).

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