Is CHD7 p.Arg1069Gly (c.3205C>G) pathogenic?

CHD7 p.Arg1069Gly (c.3205C>G) is classified Uncertain significance in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-30). AlphaMissense: likely benign (0.3044); Very rare (popmax 8.48e-05%, nfe); Associated with CHD7-related disorder.

What condition is associated with CHD7 p.Arg1069Gly (c.3205C>G)?

CHD7 p.Arg1069Gly (c.3205C>G) is associated with CHD7-related disorder (ClinVar).

How common is CHD7 p.Arg1069Gly (c.3205C>G) in the general population?

CHD7 p.Arg1069Gly (c.3205C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CHD7 p.Arg1069Gly (c.3205C>G)?

AlphaMissense predicts likely benign (score 0.3044) — an in-silico prediction, not a clinical call.

CHD7 p.Arg1069Gly

c.3205C>G · rs886040985 · VCV2631753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3044 · ACMG-weighted

gnomAD v4.1

Rare

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

Conditions

CHD7-related disorder

Computational evidence

Protein change
AlphaMissense	0.3044	likely benign
REVEL	0.589	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 14 kb · p 1.9e-20 · regional, not allelic
Overall
CADD	24.2	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 8.48e-05% European (non-Finnish) · 1/1,178,924 alleles

Overall 6.2e-05% 1/1,612,784 alleles · very rare exomes 1/1,460,556 · genomes 0/152,228 · joint denominator

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.Arg1069Gly
Coding: c.3205C>G
MANE Select: NM_017780
dbSNP: rs886040985
Type: single nucleotide variant
Location: chr8:60823843 (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

CHD7-related disorder

Similar variants

CHD7 p.Arg1069Ter Pathogenic ★★ same residue
CHD7 p.Arg1069Pro Uncertain significance ★ ⚠ same residue
CHD7 p.Arg1069= Likely benign ★ same residue
CHD7 p.Arg1069Gln Likely benign ★ same residue
CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2958-3A>G Likely pathogenic ★★ same condition
CHD7 c.4185+1G>A Pathogenic ★★ same condition
CHD7 c.5210+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-arg1069gly (accessed [today's date]).

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