Is CHD7 p.Pro2797Ser (c.8389C>T) pathogenic?

CHD7 p.Pro2797Ser (c.8389C>T) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-01). AlphaMissense: likely pathogenic (0.581); Ultra-rare (popmax 0.0871%, amr); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Pro2797Ser (c.8389C>T)?

CHD7 p.Pro2797Ser (c.8389C>T) is associated with Inborn genetic diseases, CHARGE syndrome, hypogonadotropic hypogonadism 5 with or without anosmia (ClinVar).

How common is CHD7 p.Pro2797Ser (c.8389C>T) in the general population?

CHD7 p.Pro2797Ser (c.8389C>T) is ultra-rare (popmax 0.0871%, amr) (gnomAD).

What do computational predictors say about CHD7 p.Pro2797Ser (c.8389C>T)?

AlphaMissense predicts likely pathogenic (score 0.581) — an in-silico prediction, not a clinical call.

CHD7 p.Pro2797Ser

c.8389C>T · rs769500488 · VCV696162

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.581 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0871%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.581	likely pathogenic
REVEL	0.486	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 870 bp · p 0.43 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.0871% Admixed American · 52/59,728 alleles

Filtering AF 0.0682% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00341% 55/1,612,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0871%	1,149
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.00017%	589,654

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.Pro2797Ser
Coding: c.8389C>T
MANE Select: NM_017780
dbSNP: rs769500488
Type: single nucleotide variant
Location: chr8:60865328 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CHARGE syndrome hypogonadotropic hypogonadism 5 with or without anosmia

Similar variants

CHD7 p.Pro2797= Likely benign ★ 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-pro2797ser (accessed [today's date]).

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