Is CHD8 p.Glu2104= (c.6312G>A) pathogenic?

CHD8 p.Glu2104= (c.6312G>A) is classified Benign/Likely benign in CHD8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.811%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHD8 p.Glu2104= (c.6312G>A)?

CHD8 p.Glu2104= (c.6312G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CHD8 p.Glu2104= (c.6312G>A) in the general population?

CHD8 p.Glu2104= (c.6312G>A) is rare (popmax 0.811%, eas) (gnomAD).

CHD8 p.Glu2104=

c.6312G>A · rs118140634 · VCV588887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.811%, eas)

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 0.13	GERP -2.9, phastCons 0.81
Overall
CADD	3.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.811% East Asian · 344/42,440 alleles

Filtering AF 0.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.712%

Overall 0.028% 438/1,566,598 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.811%	123
Remaining individualsnot grpmax-eligible	0.109%	920
African / African-American	0.0283%	3,528
Admixed American	0.00381%	26,213
Ashkenazi Jewishnot grpmax-eligible	0.00352%	28,430
South Asian	0.00117%	85,352
European (non-Finnish)	0.00026%	385,009

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.Glu2104=
Coding: c.6312G>A
MANE Select: NM_001170629
dbSNP: rs118140634
Type: single nucleotide variant
Location: chr14:21393483 (GRCh38)
Gene constraint: LOEUF 0.154 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.17 · 2 PDB
Residue 2104: the 'interaction with fam124b' region; the 'disordered' region

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.Glu2104Ala Uncertain significance ★ ⚠ same residue
CHD8 p.Glu2104Lys 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

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-glu2104 (accessed [today's date]).

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