Is CHD8 p.Ser2069= (c.6207G>A) pathogenic?

CHD8 p.Ser2069= (c.6207G>A) is classified Benign/Likely benign in CHD8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.142%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD8 p.Ser2069= (c.6207G>A)?

CHD8 p.Ser2069= (c.6207G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHD8 p.Ser2069= (c.6207G>A) in the general population?

CHD8 p.Ser2069= (c.6207G>A) is rare (popmax 0.142%, nfe) (gnomAD).

CHD8 p.Ser2069=

c.6207G>A · rs370827611 · VCV589731

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.142%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.015, phastCons 1
Overall
CADD	12.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% European (non-Finnish) · 1,672/1,179,724 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.111% 1,786/1,613,298 alleles · rare exomes 1,669/1,461,208 · genomes 117/152,090 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.142%	706
Remaining individualsnot grpmax-eligible	0.106%	946
African / African-American	0.0294%	3,404
Finnishnot grpmax-eligible	0.0172%	5,814
Middle Eastern	0.0164%	6,082
East Asian	0.00892%	11,212
South Asian	0.0088%	11,367
Admixed American	0.00334%	29,958

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: CHD8
Protein: p.Ser2069=
Coding: c.6207G>A
MANE Select: NM_001170629
dbSNP: rs370827611
Type: single nucleotide variant
Location: chr14:21393588 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 2069: the 'interaction with fam124b' region; the 'disordered' region; a modified residue (phosphoserine)

Full CHD8 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

Similar variants

CHD8 p.Ser2069Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD8 c.3882+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD8 p.Arg1462Ter Pathogenic ★★ same condition
CHD8 p.Arg1582Ter Pathogenic/Likely pathogenic ★★ same condition
CHD8 p.Arg2217Ter Pathogenic ★★ same condition
CHD8 p.Arg243Ter Pathogenic ★★ same condition
CHD8 c.4921+4C>T Uncertain significance ★★ same condition
CHD8 c.-1G>A Uncertain significance ★★ 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/chd8-p-ser2069 (accessed [today's date]).

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