Is CHD7 p.Asp652fs (c.1953dup) pathogenic?

CHD7 p.Asp652fs (c.1953dup) is classified Pathogenic/Likely pathogenic in CHD7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-08-21). Very rare (popmax 0.00118%, sas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Asp652fs (c.1953dup)?

CHD7 p.Asp652fs (c.1953dup) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Asp652fs (c.1953dup) in the general population?

CHD7 p.Asp652fs (c.1953dup) is very rare (popmax 0.00118%, sas) (gnomAD).

CHD7 p.Asp652fs

c.1953dup · rs2150669843 · VCV1069874

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00118%, sas)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -2.7, phastCons 1
Region caveats
Repeat context	tandem	A-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00118% South Asian · 1/84,706 alleles

Overall 7.09e-05% 1/1,410,572 alleles · very rare

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.Asp652fs
Coding: c.1953dup
MANE Select: NM_017780
dbSNP: rs2150669843
Type: Duplication
Location: chr8:60781280 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 652: the 'disordered' region

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.Asp652Glu Likely benign ★ same residue
CHD7 p.Asp2988fs Pathogenic/Likely pathogenic ★★ same condition
CHD7 p.Glu664fs Pathogenic ★★ same condition
CHD7 p.Leu2916fs Pathogenic/Likely pathogenic ★★ same condition
CHD7 p.Lys643fs Pathogenic ★★ same condition
CHD7 p.Tyr2601fs Pathogenic/Likely pathogenic ★★ same condition
CHD7 p.Tyr2601Ter Pathogenic ★★ same condition
CHD7 p.Asn2818dup Uncertain significance ★★ 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-asp652fs (accessed [today's date]).

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