Is CHD7 p.His68= (c.204T>C) pathogenic?

CHD7 p.His68= (c.204T>C) is classified Likely benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). Very rare (popmax 0.00167%, amr); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.His68= (c.204T>C)?

CHD7 p.His68= (c.204T>C) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.His68= (c.204T>C) in the general population?

CHD7 p.His68= (c.204T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

CHD7 p.His68=

c.204T>C · VCV4767614

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 0.12	GERP -2.3, phastCons 0.98
Overall
CADD	5.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Overall 6.2e-05% 1/1,613,772 alleles · very rare exomes 1/1,461,432 · genomes 0/152,340 · joint denominator

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.His68=
Coding: c.204T>C
MANE Select: NM_017780
Type: single nucleotide variant
Location: chr8:60741636 (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.His68Tyr Uncertain significance ★★ ⚠ same residue
CHD7 p.His68Asn Uncertain significance ★ ⚠ same residue
CHD7 p.His68fs 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

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-his68 (accessed [today's date]).

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