Is CHD7 p.Pro2072= (c.6216C>G) pathogenic?

CHD7 p.Pro2072= (c.6216C>G) is classified Conflicting classifications of pathogenicity in CHD7 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0976%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Pro2072= (c.6216C>G)?

CHD7 p.Pro2072= (c.6216C>G) is associated with Inborn genetic diseases, CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Pro2072= (c.6216C>G) in the general population?

CHD7 p.Pro2072= (c.6216C>G) is ultra-rare (popmax 0.0976%, nfe) (gnomAD).

CHD7 p.Pro2072=

c.6216C>G · rs199828744 · VCV95801

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0976%, nfe)

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 -5.5	GERP -3.9
Overall
CADD	0.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0976% European (non-Finnish) · 1,152/1,179,878 alleles

Filtering AF 0.0929% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0911%

Overall 0.0764% 1,233/1,613,950 alleles · ultra-rare exomes 1,177/1,461,710 · genomes 56/152,240 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0976%	1,024
Remaining individualsnot grpmax-eligible	0.072%	1,389
Admixed American	0.03%	3,334
Middle Eastern	0.0165%	6,060
African / African-American	0.0147%	6,821
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
South Asian	0.00329%	30,361

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.Pro2072=
Coding: c.6216C>G
MANE Select: NM_017780
dbSNP: rs199828744
Type: single nucleotide variant
Location: chr8:60852941 (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

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

Also linked: CHARGE syndrome hypogonadotropic hypogonadism 5 with or without anosmia

Similar variants

CHD7 p.Pro2072Arg Uncertain significance ★ ⚠ same residue
CHD7 p.Pro2072Ser 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

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-pro2072 (accessed [today's date]).

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