Is CHD8 p.Ala1669= (c.5007A>G) pathogenic?

CHD8 p.Ala1669= (c.5007A>G) is classified Benign in CHD8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.41%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHD8 p.Ala1669= (c.5007A>G)?

CHD8 p.Ala1669= (c.5007A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHD8 p.Ala1669= (c.5007A>G) in the general population?

CHD8 p.Ala1669= (c.5007A>G) is low-frequency (popmax 3.41%, afr) (gnomAD).

CHD8 p.Ala1669=

c.5007A>G · rs61752837 · VCV587908

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.41%, afr)

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 -0.27	GERP -4.4, phastCons 0.45
Overall
CADD	9.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.41% African / African-American · 2,556/75,054 alleles

Filtering AF 3.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.25%

Overall 2.38% 38,353/1,613,344 alleles · low-frequency exomes 34,587/1,461,038 · genomes 3,766/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.41%	29
Finnishnot grpmax-eligible	2.75%	36
European (non-Finnish)	2.6%	38
Remaining individualsnot grpmax-eligible	2%	50
Ashkenazi Jewishnot grpmax-eligible	1.66%	60
South Asian	1.17%	85
Admixed American	0.879%	114
Middle Eastern	0.792%	126
Amishnot grpmax-eligible	0.11%	912
East Asian	0.0134%	7,477

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.Ala1669=
Coding: c.5007A>G
MANE Select: NM_001170629
dbSNP: rs61752837
Type: single nucleotide variant
Location: chr14:21397867 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB

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 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
CHD8 p.Ala1960Thr 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-ala1669 (accessed [today's date]).

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