Is CHD7 p.Pro656= (c.1968G>A) pathogenic?

CHD7 p.Pro656= (c.1968G>A) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00239%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Pro656= (c.1968G>A)?

CHD7 p.Pro656= (c.1968G>A) is associated with Inborn genetic diseases, CHARGE syndrome (ClinVar).

How common is CHD7 p.Pro656= (c.1968G>A) in the general population?

CHD7 p.Pro656= (c.1968G>A) is very rare (popmax 0.00239%, eas) (gnomAD).

CHD7 p.Pro656=

c.1968G>A · rs569213080 · VCV589565

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00239%, eas)

Conditions

Inborn genetic diseases

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 4.8	GERP -0.34, phastCons 1
Overall
CADD	14.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% East Asian · 1/41,868 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000447% 7/1,566,404 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00328%	30,449
East Asiangrpmax	0.00239%	41,868
African / African-American	0.00136%	73,382
South Asian	0.00118%	84,836
European (non-Finnish)	0.000173%	578,162

Remaining individuals 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.Pro656=
Coding: c.1968G>A
MANE Select: NM_017780
dbSNP: rs569213080
Type: single nucleotide variant
Location: chr8:60781302 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 656: the 'disordered' region

Full CHD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CHARGE syndrome

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-pro656 (accessed [today's date]).

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