Is CHD7 p.His368= (c.1104C>T) pathogenic?

CHD7 p.His368= (c.1104C>T) is classified Conflicting classifications of pathogenicity in CHD7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-11). Ultra-rare (popmax 0.0516%, sas); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.His368= (c.1104C>T)?

CHD7 p.His368= (c.1104C>T) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.His368= (c.1104C>T) in the general population?

CHD7 p.His368= (c.1104C>T) is ultra-rare (popmax 0.0516%, sas) (gnomAD).

CHD7 p.His368=

c.1104C>T · rs763250461 · VCV284635

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, sas)

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 4.1	GERP 1.7, phastCons 1
Overall
CADD	8.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0516% South Asian · 47/91,078 alleles

Filtering AF 0.0399% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00322% 52/1,614,026 alleles · ultra-rare exomes 50/1,461,710 · genomes 2/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0516%	1,938
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	8.48e-05%	1,179,906

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.His368=
Coding: c.1104C>T
MANE Select: NM_017780
dbSNP: rs763250461
Type: single nucleotide variant
Location: chr8:60742536 (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 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-his368 (accessed [today's date]).

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