Is CHD7 p.Arg1069Gln (c.3206G>A) pathogenic?

CHD7 p.Arg1069Gln (c.3206G>A) is classified Likely benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely benign (0.1117); Very rare (popmax 0.00229%, nfe); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Arg1069Gln (c.3206G>A)?

CHD7 p.Arg1069Gln (c.3206G>A) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Arg1069Gln (c.3206G>A) in the general population?

CHD7 p.Arg1069Gln (c.3206G>A) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about CHD7 p.Arg1069Gln (c.3206G>A)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

CHD7 p.Arg1069Gln

c.3206G>A · rs1346050533 · VCV836902

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Conditions

CHARGE syndrome

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.463	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 14 kb · p 1.9e-20 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,178,892 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00174% 28/1,612,644 alleles · very rare exomes 27/1,460,492 · genomes 1/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,663
East Asian	0.00223%	44,890

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: CHD7
Protein: p.Arg1069Gln
Coding: c.3206G>A
MANE Select: NM_017780
dbSNP: rs1346050533
Type: single nucleotide variant
Location: chr8:60823844 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1069: the helicase atp-binding domain

Full CHD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHARGE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD7 p.Arg1069Ter Pathogenic ★★ same residue
CHD7 p.Arg1069Pro Uncertain significance ★ ⚠ same residue
CHD7 p.Arg1069= Likely benign ★ same residue
CHD7 p.Arg1069Gly Uncertain significance ★ same residue
CHD7 c.2097-2A>G Pathogenic ★★ same condition
CHD7 c.2238+1G>A Pathogenic ★★ same condition
CHD7 c.2377-1G>A Likely pathogenic ★★ same condition
CHD7 c.2613+1G>A 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/chd7-p-arg1069gln (accessed [today's date]).

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