Is CHD3 p.Arg1266Trp (c.3796C>T) pathogenic?

CHD3 p.Arg1266Trp (c.3796C>T) is classified Uncertain significance in CHD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.9813); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Arg1266Trp (c.3796C>T)?

CHD3 p.Arg1266Trp (c.3796C>T) is associated with Inborn genetic diseases, Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Arg1266Trp (c.3796C>T) in the general population?

CHD3 p.Arg1266Trp (c.3796C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHD3 p.Arg1266Trp (c.3796C>T)?

AlphaMissense predicts likely pathogenic (score 0.9813) — an in-silico prediction, not a clinical call.

CHD3 p.Arg1266Trp

c.3796C>T · VCV3491958

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9813 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9813	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -14.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.3, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 3,550 bp · p 4.9e-38 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.84e-05% 1/1,461,886 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.Arg1266Trp
Coding: c.3796C>T
MANE Select: NM_001005273
Type: single nucleotide variant
Location: chr17:7903893 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1266: a UniProt-annotated variant site (in snibcps)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Snijders Blok-Campeau syndrome

Similar variants

CHD3 p.Arg1266Gln Uncertain significance ★★ ⚠ same residue
CHD3 p.Arg1266= Likely benign same residue
CHD3 c.4073-2A>C Likely pathogenic ★★ same condition
CHD3 p.Arg103Ter 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

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-arg1266trp (accessed [today's date]).

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