Is CHD7 p.Ala2Glu (c.5C>A) pathogenic?

CHD7 p.Ala2Glu (c.5C>A) is classified Likely pathogenic in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-08). AlphaMissense: likely pathogenic (0.9181); No allele count reported in gnomAD v4.1 (AN 1,600,592); Associated with hypogonadotropic hypogonadism 5 with or without anosmia.

What condition is associated with CHD7 p.Ala2Glu (c.5C>A)?

CHD7 p.Ala2Glu (c.5C>A) is associated with hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Ala2Glu (c.5C>A) in the general population?

CHD7 p.Ala2Glu (c.5C>A) is no allele count reported in gnomAD v4.1 (AN 1,600,592) (gnomAD).

What do computational predictors say about CHD7 p.Ala2Glu (c.5C>A)?

AlphaMissense predicts likely pathogenic (score 0.9181) — an in-silico prediction, not a clinical call.

CHD7 p.Ala2Glu

c.5C>A · rs1809000474 · VCV1028059

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9181 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,592)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hypogonadotropic hypogonadism 5 with or without anosmia

Computational evidence

Protein change
AlphaMissense	0.9181	likely pathogenic ✓ concordant with ClinVar
REVEL	0.245	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.84 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,592). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD7
Protein: p.Ala2Glu
Coding: c.5C>A
MANE Select: NM_017780
dbSNP: rs1809000474
Type: single nucleotide variant
Location: chr8:60741437 (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

Similar variants

CHD7 p.Ala2Gly Uncertain significance ★ ⚠ same residue
CHD7 p.Ala2= Likely benign ★ same residue
CHD7 c.4353+1G>T Pathogenic ★★ same condition
CHD7 c.5405-17G>A Pathogenic ★★ same condition
CHD7 c.5405-7G>A Pathogenic ★★ same condition
CHD7 p.Arg1069Ter Pathogenic ★★ same condition
CHD7 p.Arg1677Ter Pathogenic ★★ same condition
CHD7 p.Arg2053Ter 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-ala2glu (accessed [today's date]).

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