Is CHD3 p.Pro538fs (c.1612_1613delinsA) pathogenic?

CHD3 p.Pro538fs (c.16121613delinsA) is classified Pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-10). Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Pro538fs (c.1612_1613delinsA)?

CHD3 p.Pro538fs (c.1612_1613delinsA) is associated with Snijders Blok-Campeau syndrome (ClinVar).

CHD3 p.Pro538fs

c.1612_1613delinsA · VCV3376968

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 10 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -3.5, phastCons 0.53

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

Variant & gene context

Gene: CHD3
Protein: p.Pro538fs
Coding: c.1612_1613delinsA
MANE Select: NM_001005273
Type: Indel
Location: chr17:7895447 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 538: the chromo 1 domain; the 'disordered' region; a UniProt-annotated variant site (in snibcps)

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.Pro538Leu Uncertain significance ★ ⚠ same residue
CHD3 c.4073-3delinsAA Pathogenic ★ same condition
CHD3 p.Asn1359_Gln1360delinsLysTrpGlyTrpSer Likely pathogenic ★ same condition
CHD3 p.Asp1120His Likely pathogenic ★ same condition
CHD3 p.Phe73delinsLeuPro Uncertain significance ★ same condition
CHD3 p.Pro538Ala Uncertain significance ★ ⚠ same residue
CHD3 p.Pro538Arg Uncertain significance ★ ⚠ same residue
CHD3 p.Ser1284Ile Uncertain significance ★ 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-pro538fs (accessed [today's date]).

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