Is CHD7 p.Pro1813= (c.5439C>T) pathogenic?

CHD7 p.Pro1813= (c.5439C>T) is classified Conflicting classifications of pathogenicity in CHD7 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.229%, sas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Pro1813= (c.5439C>T)?

CHD7 p.Pro1813= (c.5439C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Pro1813= (c.5439C>T) in the general population?

CHD7 p.Pro1813= (c.5439C>T) is rare (popmax 0.229%, sas) (gnomAD).

CHD7 p.Pro1813=

c.5439C>T · rs373869399 · VCV166868

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.229%, sas)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3	GERP -3.9
Overall
CADD	7.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.229% South Asian · 208/90,972 alleles

Filtering AF 0.203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.193%

Overall 0.0178% 288/1,613,640 alleles · rare exomes 266/1,461,314 · genomes 22/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.229%	437
Remaining individualsnot grpmax-eligible	0.024%	4,165
East Asian	0.0156%	6,408
African / African-American	0.0107%	9,382
European (non-Finnish)	0.00415%	24,076
Finnishnot grpmax-eligible	0.00156%	63,988

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.Pro1813=
Coding: c.5439C>T
MANE Select: NM_017780
dbSNP: rs373869399
Type: single nucleotide variant
Location: chr8:60850527 (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

CHARGE syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD7 p.Pro1813Ser Uncertain significance ★★ same residue
CHD7 p.Pro1813Leu 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

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-pro1813 (accessed [today's date]).

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