Is CHD7 p.Arg944Ser (c.2830C>A) pathogenic?

CHD7 p.Arg944Ser (c.2830C>A) is classified Uncertain significance in CHD7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-29). AlphaMissense: ambiguous (0.364); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Arg944Ser (c.2830C>A)?

CHD7 p.Arg944Ser (c.2830C>A) is associated with Inborn genetic diseases, CHARGE syndrome (ClinVar).

How common is CHD7 p.Arg944Ser (c.2830C>A) in the general population?

CHD7 p.Arg944Ser (c.2830C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CHD7 p.Arg944Ser (c.2830C>A)?

AlphaMissense predicts ambiguous (score 0.364) — an in-silico prediction, not a clinical call.

CHD7 p.Arg944Ser

c.2830C>A · rs587783435 · VCV158286

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.364 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.364	ambiguous
REVEL	0.893	moderately pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 5.2e-06 · regional, not allelic
Overall
CADD	23.6	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 8.48e-05% European (non-Finnish) · 1/1,179,496 alleles

Overall 6.2e-05% 1/1,612,936 alleles · very rare exomes 1/1,460,960 · genomes 0/151,976 · joint denominator

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.Arg944Ser
Coding: c.2830C>A
MANE Select: NM_017780
dbSNP: rs587783435
Type: single nucleotide variant
Location: chr8:60821922 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 944: the 'disordered' region; a UniProt-annotated variant site (in charges; uncertain significance); a UniProt-annotated variant site (in hh5); the chromo 2 domain

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

Similar variants

CHD7 p.Arg944His Benign/Likely benign ★★ same residue
CHD7 p.Arg944Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg944ser (accessed [today's date]).

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