Is CHD7 p.Ala99= (c.297G>A) pathogenic?

CHD7 p.Ala99= (c.297G>A) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-25). Ultra-rare (popmax 0.0167%, amr); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ala99= (c.297G>A)?

CHD7 p.Ala99= (c.297G>A) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ala99= (c.297G>A) in the general population?

CHD7 p.Ala99= (c.297G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

CHD7 p.Ala99=

c.297G>A · rs775823361 · VCV1128160

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -5
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,004 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.0013% 21/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
East Asian	0.00223%	44,886
European (non-Finnish)	0.000848%	117,987

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.Ala99=
Coding: c.297G>A
MANE Select: NM_017780
dbSNP: rs775823361
Type: single nucleotide variant
Location: chr8:60741729 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 99: the 'disordered' region; a UniProt-annotated variant site (in charges; uncertain significance)

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.Ala99Thr Benign/Likely benign ★★ same residue
CHD7 p.Ala99Gly Uncertain significance ★ ⚠ same residue
CHD7 p.Ala99Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD7 p.Ala99Ser Uncertain significance ★ ⚠ same residue
CHD7 p.Ala99Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala99 (accessed [today's date]).

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