Is CHD2 p.Lys203Arg (c.608A>G) pathogenic?

CHD2 p.Lys203Arg (c.608A>G) is classified Benign/Likely benign in CHD2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0617); Rare (popmax 0.451%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Lys203Arg (c.608A>G)?

CHD2 p.Lys203Arg (c.608A>G) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Lys203Arg (c.608A>G) in the general population?

CHD2 p.Lys203Arg (c.608A>G) is rare (popmax 0.451%, nfe) (gnomAD).

What do computational predictors say about CHD2 p.Lys203Arg (c.608A>G)?

AlphaMissense predicts likely benign (score 0.0617) — an in-silico prediction, not a clinical call.

CHD2 p.Lys203Arg

c.608A>G · rs117844037 · VCV257714

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.0617 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.451%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0617	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 11 kb · p 0.18 · regional, not allelic
Overall
CADD	17.17	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 0.451% European (non-Finnish) · 5,319/1,180,016 alleles

Filtering AF 0.441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.436%

Overall 0.359% 5,791/1,614,170 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.451%	222
Remaining individualsnot grpmax-eligible	0.339%	295
Finnishnot grpmax-eligible	0.242%	413
Amishnot grpmax-eligible	0.219%	456
Admixed American	0.0916%	1,091
African / African-American	0.056%	1,786
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
East Asian	0.00223%	44,886
South Asian	0.0011%	91,086

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: CHD2
Protein: p.Lys203Arg
Coding: c.608A>G
MANE Select: NM_001271
dbSNP: rs117844037
Type: single nucleotide variant
Location: chr15:92939634 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 203: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'disordered' region

Full CHD2 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

Also linked: developmental and epileptic encephalopathy 94

Similar variants

CHD2 p.Lys203Ile Uncertain significance ★★ ⚠ same residue
CHD2 p.Lys203Glu Uncertain significance ★ ⚠ same residue
CHD2 c.1153+1G>C Pathogenic ★★ same condition
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.294+1G>T Likely pathogenic ★★ same condition
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 c.693-1G>A Likely pathogenic ★★ same condition
CHD2 p.Ala879Val 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/chd2-p-lys203arg (accessed [today's date]).

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