Is CHD7 p.Pro674= (c.2022T>C) pathogenic?

CHD7 p.Pro674= (c.2022T>C) is classified Likely benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-10). No allele count reported in gnomAD v4.1 (AN 1,555,640); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Pro674= (c.2022T>C)?

CHD7 p.Pro674= (c.2022T>C) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Pro674= (c.2022T>C) in the general population?

CHD7 p.Pro674= (c.2022T>C) is no allele count reported in gnomAD v4.1 (AN 1,555,640) (gnomAD).

CHD7 p.Pro674=

c.2022T>C · rs2487540599 · VCV2799149

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,555,640)

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 0.63	GERP -2.1, phastCons 1
Overall
CADD	8.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,555,640). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD7
Protein: p.Pro674=
Coding: c.2022T>C
MANE Select: NM_017780
dbSNP: rs2487540599
Type: single nucleotide variant
Location: chr8:60781356 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 674: 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.Pro674Arg Likely benign ★ 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-pro674 (accessed [today's date]).

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