Is CHD3 p.Arg412Gln (c.1235G>A) pathogenic?

CHD3 p.Arg412Gln (c.1235G>A) is classified Conflicting classifications of pathogenicity in CHD3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-08-01). AlphaMissense: likely benign (0.1272); Ultra-rare (popmax 0.0164%, mid); Associated with Snijders Blok-Campeau syndrome.

What condition is associated with CHD3 p.Arg412Gln (c.1235G>A)?

CHD3 p.Arg412Gln (c.1235G>A) is associated with Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Arg412Gln (c.1235G>A) in the general population?

CHD3 p.Arg412Gln (c.1235G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CHD3 p.Arg412Gln (c.1235G>A)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

CHD3 p.Arg412Gln

c.1235G>A · rs147796138 · VCV2567607

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Snijders Blok-Campeau syndrome

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -0.54, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 1,204 bp · p 3.2e-11 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.0134% 216/1,613,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,679
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.0159%	6,276
African / African-American	0.0107%	9,356
Admixed American	0.00667%	14,996
South Asian	0.00329%	30,355
East Asian	0.00223%	44,876

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.Arg412Gln
Coding: c.1235G>A
MANE Select: NM_001005273
dbSNP: rs147796138
Type: single nucleotide variant
Location: chr17:7894574 (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 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-arg412gln (accessed [today's date]).

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