Is CHD7 p.Ile491= (c.1473C>T) pathogenic?

CHD7 p.Ile491= (c.1473C>T) is classified Benign/Likely benign in CHD7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-07). Very rare (popmax 0.00446%, eas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ile491= (c.1473C>T)?

CHD7 p.Ile491= (c.1473C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ile491= (c.1473C>T) in the general population?

CHD7 p.Ile491= (c.1473C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

CHD7 p.Ile491=

c.1473C>T · rs182294889 · VCV1535397

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 1.6, phastCons 1
Overall
CADD	10.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,830 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0109% 175/1,612,502 alleles · very rare exomes 149/1,460,210 · genomes 26/152,292 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.224%	447
Remaining individualsnot grpmax-eligible	0.0128%	7,805
East Asiangrpmax	0.00446%	22,415
European (non-Finnish)	0.00187%	53,599

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile491=
Coding: c.1473C>T
MANE Select: NM_017780
dbSNP: rs182294889
Type: single nucleotide variant
Location: chr8:60742905 (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

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

Similar variants

CHD7 p.Ile491Asn 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
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
CHD7 c.2957+2T>C 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-ile491 (accessed [today's date]).

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