Is CHD7 p.His237= (c.711C>T) pathogenic?

CHD7 p.His237= (c.711C>T) is classified Likely benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Ultra-rare (popmax 0.0825%, mid); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.His237= (c.711C>T)?

CHD7 p.His237= (c.711C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.His237= (c.711C>T) in the general population?

CHD7 p.His237= (c.711C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

CHD7 p.His237=

c.711C>T · rs1188337353 · VCV1111152

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

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 -5.1	GERP -5
Overall
CADD	4.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00112% 18/1,613,938 alleles · ultra-rare exomes 13/1,461,670 · genomes 5/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
East Asian	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00133%	75,042
South Asian	0.0011%	91,084
European (non-Finnish)	0.000763%	131,095

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.His237=
Coding: c.711C>T
MANE Select: NM_017780
dbSNP: rs1188337353
Type: single nucleotide variant
Location: chr8:60742143 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 237: 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.His237Tyr Uncertain significance ★ ⚠ same residue
CHD7 p.His237fs Likely 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-his237 (accessed [today's date]).

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