Is CHD3 p.Arg1706Trp (c.5116C>T) pathogenic?

CHD3 p.Arg1706Trp (c.5116C>T) is classified Uncertain significance in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-13). AlphaMissense: likely pathogenic (0.5896); Very rare (popmax 0.00223%, eas); Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Arg1706Trp (c.5116C>T)?

CHD3 p.Arg1706Trp (c.5116C>T) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Arg1706Trp (c.5116C>T) in the general population?

CHD3 p.Arg1706Trp (c.5116C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CHD3 p.Arg1706Trp (c.5116C>T)?

AlphaMissense predicts likely pathogenic (score 0.5896) — an in-silico prediction, not a clinical call.

CHD3 p.Arg1706Trp

c.5116C>T · rs903965338 · VCV2439977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
AlphaMissense	0.5896	likely pathogenic
REVEL	0.673	pathogenic-leaning
SaProt	LLR -10.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP 0.56, phastCons 0.95
Regional constraint	o/e 0.95	unconstrained · MANE · 1,113 bp · p 0.44 · regional, not allelic
Overall
CADD	25.5	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 0.00223% East Asian · 1/44,788 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000869% 14/1,611,072 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,167
East Asiangrpmax	0.00223%	44,788
Finnishnot grpmax-eligible	0.00156%	64,002
African / African-American	0.00134%	74,810
European (non-Finnish)	0.000764%	130,865

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1706Trp
Coding: c.5116C>T
MANE Select: NM_001005273
dbSNP: rs903965338
Type: single nucleotide variant
Location: chr17:7907983 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1706: 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 p.Arg1706Gln Uncertain significance ★ ⚠ same residue
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

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-arg1706trp (accessed [today's date]).

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