Is CHD7 p.Ile445= (c.1335C>T) pathogenic?

CHD7 p.Ile445= (c.1335C>T) is classified Benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Ultra-rare (popmax 0.0178%, eas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ile445= (c.1335C>T)?

CHD7 p.Ile445= (c.1335C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ile445= (c.1335C>T) in the general population?

CHD7 p.Ile445= (c.1335C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

CHD7 p.Ile445=

c.1335C>T · VCV4742381

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 -4.1	GERP -5.2
Overall
CADD	3.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,906 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00347% 56/1,613,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,613
European (non-Finnish)	0.00373%	26,816
African / African-American	0.00267%	37,462
South Asian	0.0022%	45,544

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.Ile445=
Coding: c.1335C>T
MANE Select: NM_017780
Type: single nucleotide variant
Location: chr8:60742767 (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 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
CHD7 c.3202-3T>G 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-ile445 (accessed [today's date]).

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