Is CHD2 p.His690Tyr (c.2068C>T) pathogenic?

CHD2 p.His690Tyr (c.2068C>T) is classified Likely pathogenic in CHD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-10). AlphaMissense: likely pathogenic (0.9727); Absent from gnomAD v4.1; Associated with complex neurodevelopmental disorder.

What condition is associated with CHD2 p.His690Tyr (c.2068C>T)?

CHD2 p.His690Tyr (c.2068C>T) is associated with complex neurodevelopmental disorder (ClinVar).

How common is CHD2 p.His690Tyr (c.2068C>T) in the general population?

CHD2 p.His690Tyr (c.2068C>T) is absent from gnomAD v4.1 (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CHD2 p.His690Tyr (c.2068C>T)?

AlphaMissense predicts likely pathogenic (score 0.9727) — an in-silico prediction, not a clinical call.

CHD2 p.His690Tyr

c.2068C>T · rs2053779726 · VCV984848

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9727 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9727	likely pathogenic ✓ concordant with ClinVar
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -11.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 18 kb · p 1e-19 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD2
Protein: p.His690Tyr
Coding: c.2068C>T
MANE Select: NM_001271
dbSNP: rs2053779726
Type: single nucleotide variant
Location: chr15:92967392 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 690: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance)

Full CHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complex neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

CHD2 p.His690= Likely benign ★ same residue
CHD2 p.Arg900Gln Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Asp1042Glu Likely benign ★★ same condition
CHD2 p.Pro1353Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD2 p.Pro182Ala Uncertain significance ★ ⚠ same condition
CHD2 p.Trp1261Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
CHD2 p.Ser988Ter Pathogenic same condition
CHD2 p.Gln1392fs 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/chd2-p-his690tyr (accessed [today's date]).

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