Is CHD7 p.Pro2036= (c.6108G>A) pathogenic?

CHD7 p.Pro2036= (c.6108G>A) is classified Benign/Likely benign in CHD7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0367%, amr); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Pro2036= (c.6108G>A)?

CHD7 p.Pro2036= (c.6108G>A) is associated with CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Pro2036= (c.6108G>A) in the general population?

CHD7 p.Pro2036= (c.6108G>A) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

CHD7 p.Pro2036=

c.6108G>A · rs372755547 · VCV385046

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Conditions

CHARGE syndrome

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 -6.4	GERP -3.9
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/59,978 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00422% 68/1,611,474 alleles · ultra-rare exomes 52/1,459,368 · genomes 16/152,106 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,726
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00802%	12,474
South Asian	0.00549%	18,215
European (non-Finnish)	0.0028%	35,701
East Asian	0.00223%	44,820
Finnishnot grpmax-eligible	0.00157%	63,630

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.Pro2036=
Coding: c.6108G>A
MANE Select: NM_017780
dbSNP: rs372755547
Type: single nucleotide variant
Location: chr8:60852833 (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

Also linked: hypogonadotropic hypogonadism 5 with or without anosmia

Similar variants

CHD7 p.Pro2036Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro2036 (accessed [today's date]).

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