Is CHD3 p.Val7fs (c.20_21del) pathogenic?

CHD3 p.Val7fs (c.2021del) is classified Pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-08). Very rare (popmax 0.00133%, afr); Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Val7fs (c.20_21del)?

CHD3 p.Val7fs (c.20_21del) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Val7fs (c.20_21del) in the general population?

CHD3 p.Val7fs (c.20_21del) is very rare (popmax 0.00133%, afr) (gnomAD).

CHD3 p.Val7fs

c.20_21del · rs2544690565 · VCV1802176

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Snijders Blok-Campeau syndrome

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -0.94, phastCons 0.004

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,044 alleles

Overall 0.000124% 2/1,614,222 alleles · very rare exomes 2/1,461,880 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,044
European (non-Finnish)	8.47e-05%	1,180,038

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHD3
Protein: p.Val7fs
Coding: c.20_21del
MANE Select: NM_001005273
dbSNP: rs2544690565
Type: Microsatellite
Location: chr17:7889018 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Snijders Blok-Campeau syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD3 p.Arg933fs Likely pathogenic ★ same condition
CHD3 p.Gln1438fs Likely pathogenic ★ same condition
CHD3 p.Gly1109del Uncertain significance ★ same condition
CHD3 p.Pro82_Leu83insProPro Uncertain significance ★ same condition
CHD3 c.4073-2A>C Likely pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Gln Pathogenic/Likely pathogenic ★★ 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/chd3-p-val7fs (accessed [today's date]).

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