Is CHD7 p.Ser2295= (c.6885A>G) pathogenic?

CHD7 p.Ser2295= (c.6885A>G) is classified Likely benign in CHD7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-03). Ultra-rare (popmax 0.0386%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHD7 p.Ser2295= (c.6885A>G)?

CHD7 p.Ser2295= (c.6885A>G) is associated with Inborn genetic diseases, CHARGE syndrome (ClinVar).

How common is CHD7 p.Ser2295= (c.6885A>G) in the general population?

CHD7 p.Ser2295= (c.6885A>G) is ultra-rare (popmax 0.0386%, sas) (gnomAD).

CHD7 p.Ser2295=

c.6885A>G · rs752966093 · VCV588598

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.60	donor gain · deltas
Pangolin	Δ0.22	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -4.1	GERP -2.4
Overall
CADD	14.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% South Asian · 35/90,764 alleles

Filtering AF 0.0284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.00242% 39/1,611,422 alleles · ultra-rare exomes 39/1,459,062 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0386%	2,593
African / African-American	0.00267%	37,501
Remaining individualsnot grpmax-eligible	0.0016%	62,392
European (non-Finnish)	8.49e-05%	1,178,026

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.Ser2295=
Coding: c.6885A>G
MANE Select: NM_017780
dbSNP: rs752966093
Type: single nucleotide variant
Location: chr8:60854472 (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

Similar variants

CHD7 p.Ser2295fs Pathogenic ★ 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-ser2295 (accessed [today's date]).

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