Is CHD7 p.Gln489Pro (c.1466A>C) pathogenic?

CHD7 p.Gln489Pro (c.1466A>C) is classified Uncertain significance in CHD7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Gln489Pro (c.1466A>C)?

CHD7 p.Gln489Pro (c.1466A>C) is associated with Inborn genetic diseases, CHARGE syndrome (ClinVar).

How common is CHD7 p.Gln489Pro (c.1466A>C) in the general population?

CHD7 p.Gln489Pro (c.1466A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CHD7 p.Gln489Pro (c.1466A>C)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

CHD7 p.Gln489Pro

c.1466A>C · rs1809127222 · VCV1773253

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.298	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.84 · regional, not allelic
Overall
CADD	21.2	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 0.00167% Admixed American · 1/59,748 alleles

Overall 6.2e-05% 1/1,612,478 alleles · very rare exomes 1/1,460,182 · genomes 0/152,296 · 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.Gln489Pro
Coding: c.1466A>C
MANE Select: NM_017780
dbSNP: rs1809127222
Type: single nucleotide variant
Location: chr8:60742898 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full CHD7 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: CHARGE syndrome

Similar variants

CHD7 p.Gln489= Benign ★ same residue
CHD7 p.Gln489Ter Pathogenic ★★ 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
CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD7 c.2836-2A>T 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-gln489pro (accessed [today's date]).

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