Is CHD7 p.Pro2560= (c.7680C>T) pathogenic?

CHD7 p.Pro2560= (c.7680C>T) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). Ultra-rare (popmax 0.0167%, amr); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Pro2560= (c.7680C>T)?

CHD7 p.Pro2560= (c.7680C>T) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Pro2560= (c.7680C>T) in the general population?

CHD7 p.Pro2560= (c.7680C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

CHD7 p.Pro2560=

c.7680C>T · rs761548538 · VCV696605

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

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 -1.5	GERP -3.6
Overall
CADD	7.839	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,000 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00297% 48/1,613,856 alleles · ultra-rare exomes 42/1,461,700 · genomes 6/152,156 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,000
Remaining individualsnot grpmax-eligible	0.0048%	20,820
European (non-Finnish)	0.00288%	34,703
South Asian	0.0011%	91,082

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.Pro2560=
Coding: c.7680C>T
MANE Select: NM_017780
dbSNP: rs761548538
Type: single nucleotide variant
Location: chr8:60860975 (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.Pro2560Ser Conflicting classifications of pathogenicity ★ same residue
CHD7 p.Pro2560Ala 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-pro2560 (accessed [today's date]).

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