Is CHD3 p.Arg1698Ter (c.5092C>T) pathogenic?

CHD3 p.Arg1698Ter (c.5092C>T) is classified Likely pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-30). Very rare (popmax 8.48e-05%, nfe); Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Arg1698Ter (c.5092C>T)?

CHD3 p.Arg1698Ter (c.5092C>T) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Arg1698Ter (c.5092C>T) in the general population?

CHD3 p.Arg1698Ter (c.5092C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CHD3 p.Arg1698Ter

c.5092C>T · rs2545112217 · VCV2584365

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 34 of 40
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,158 alleles

Overall 6.85e-05% 1/1,460,786 alleles · very rare

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.Arg1698Ter
Coding: c.5092C>T
MANE Select: NM_001005273
dbSNP: rs2545112217
Type: single nucleotide variant
Location: chr17:7907959 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1698: the 'disordered' region; the 'required for interaction with pcnt' 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 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
CHD3 p.Arg1169Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Trp Pathogenic ★★ same condition
CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1172Trp 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-arg1698ter (accessed [today's date]).

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