Is CHD7 p.Ser2308= (c.6924G>C) pathogenic?

CHD7 p.Ser2308= (c.6924G>C) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0281%, afr); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Ser2308= (c.6924G>C)?

CHD7 p.Ser2308= (c.6924G>C) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.Ser2308= (c.6924G>C) in the general population?

CHD7 p.Ser2308= (c.6924G>C) is ultra-rare (popmax 0.0281%, afr) (gnomAD).

CHD7 p.Ser2308=

c.6924G>C · rs61733338 · VCV1601989

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, afr)

Conditions

hypogonadotropic hypogonadism 5 with or without anosmia

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 -6.1	GERP -1.9
Overall
CADD	0.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% African / African-American · 21/74,652 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.00156% 25/1,598,786 alleles · ultra-rare exomes 16/1,446,568 · genomes 9/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0281%	3,555
Remaining individualsnot grpmax-eligible	0.00162%	61,848
European (non-Finnish)	0.000257%	389,505

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.Ser2308=
Coding: c.6924G>C
MANE Select: NM_017780
dbSNP: rs61733338
Type: single nucleotide variant
Location: chr8:60854511 (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

hypogonadotropic hypogonadism 5 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CHARGE syndrome

Similar variants

CHD7 p.Ser2308Leu Conflicting classifications of pathogenicity ★ same residue
CHD7 p.Ser2308Ter 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
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-ser2308 (accessed [today's date]).

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