Is CHD3 p.Tyr95Cys (c.284A>G) pathogenic?

CHD3 p.Tyr95Cys (c.284A>G) is classified Likely benign in CHD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.1821); Very rare (popmax 0.00404%, afr); Associated with intellectual disability.

What condition is associated with CHD3 p.Tyr95Cys (c.284A>G)?

CHD3 p.Tyr95Cys (c.284A>G) is associated with intellectual disability (ClinVar).

How common is CHD3 p.Tyr95Cys (c.284A>G) in the general population?

CHD3 p.Tyr95Cys (c.284A>G) is very rare (popmax 0.00404%, afr) (gnomAD).

What do computational predictors say about CHD3 p.Tyr95Cys (c.284A>G)?

AlphaMissense predicts likely benign (score 0.1821) — an in-silico prediction, not a clinical call.

CHD3 p.Tyr95Cys

c.284A>G · rs777077851 · VCV975668

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1821	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -6.11	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,958 bp · p 0.95 · regional, not allelic
Overall
CADD	26.6	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

Grpmax group 0.00404% African / African-American · 3/74,274 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000497%

Overall 0.000373% 6/1,610,186 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,758
South Asian	0.00111%	90,164
European (non-Finnish)	0.00017%	589,477

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: CHD3
Protein: p.Tyr95Cys
Coding: c.284A>G
MANE Select: NM_001005273
dbSNP: rs777077851
Type: single nucleotide variant
Location: chr17:7890641 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 95: the 'disordered' region

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHD3 p.Tyr95His Uncertain significance ★ same residue
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Trp Pathogenic ★★ same condition
CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1342Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg985Gln Pathogenic ★★ same condition
CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Asn1159Lys Pathogenic/Likely 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/chd3-p-tyr95cys (accessed [today's date]).

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