Is CHD7 p.Ala401= (c.1203A>G) pathogenic?

CHD7 p.Ala401= (c.1203A>G) is classified Benign/Likely benign in CHD7 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.629%, eas); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Ala401= (c.1203A>G)?

CHD7 p.Ala401= (c.1203A>G) is associated with hypogonadotropic hypogonadism 5 with or without anosmia, CHARGE syndrome (ClinVar).

How common is CHD7 p.Ala401= (c.1203A>G) in the general population?

CHD7 p.Ala401= (c.1203A>G) is rare (popmax 0.629%, eas) (gnomAD).

CHD7 p.Ala401=

c.1203A>G · rs147960212 · VCV696208

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.629%, eas)

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 2.6	GERP -0.68, phastCons 1
Overall
CADD	7.578	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.629% East Asian · 282/44,854 alleles

Filtering AF 0.568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.545%

Overall 0.0192% 310/1,612,162 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.629%	159
Remaining individualsnot grpmax-eligible	0.00801%	12,482
European (non-Finnish)	0.00187%	53,573
South Asian	0.0011%	90,924

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.Ala401=
Coding: c.1203A>G
MANE Select: NM_017780
dbSNP: rs147960212
Type: single nucleotide variant
Location: chr8:60742635 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 401: the 'disordered' region

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.Ala401Thr Uncertain significance ★ ⚠ 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-ala401 (accessed [today's date]).

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