Is CHD7 p.Ser2698= (c.8094G>A) pathogenic?

CHD7 p.Ser2698= (c.8094G>A) is classified Benign in CHD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Very rare (popmax 0.00449%, eas); Associated with CHARGE syndrome.

What condition is associated with CHD7 p.Ser2698= (c.8094G>A)?

CHD7 p.Ser2698= (c.8094G>A) is associated with CHARGE syndrome (ClinVar).

How common is CHD7 p.Ser2698= (c.8094G>A) in the general population?

CHD7 p.Ser2698= (c.8094G>A) is very rare (popmax 0.00449%, eas) (gnomAD).

CHD7 p.Ser2698=

c.8094G>A · VCV3668003

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00449%, eas)

Conditions

CHARGE syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.5	GERP -3.9
Overall
CADD	7.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% East Asian · 2/44,524 alleles

Filtering AF 0.000745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000279%

Overall 0.000437% 7/1,601,890 alleles · very rare exomes 7/1,449,604 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00449%	22,262
Remaining individualsnot grpmax-eligible	0.00322%	31,023
South Asian	0.00112%	89,030
European (non-Finnish)	0.00017%	586,792

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.Ser2698=
Coding: c.8094G>A
MANE Select: NM_017780
Type: single nucleotide variant
Location: chr8:60865033 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2698: an α-helix

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.Ser2698Trp Uncertain significance ★ same residue
CHD7 p.Ser2698Leu 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

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-ser2698 (accessed [today's date]).

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