Is CHD2 p.Val1495Met (c.4483G>A) pathogenic?

CHD2 p.Val1495Met (c.4483G>A) is classified Benign/Likely benign in CHD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.2498); Ultra-rare (popmax 0.044%, afr); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Val1495Met (c.4483G>A)?

CHD2 p.Val1495Met (c.4483G>A) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

How common is CHD2 p.Val1495Met (c.4483G>A) in the general population?

CHD2 p.Val1495Met (c.4483G>A) is ultra-rare (popmax 0.044%, afr) (gnomAD).

What do computational predictors say about CHD2 p.Val1495Met (c.4483G>A)?

AlphaMissense predicts likely benign (score 0.2498) — an in-silico prediction, not a clinical call.

CHD2 p.Val1495Met

c.4483G>A · rs770993927 · VCV411857

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2498 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.044%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2498	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 111 bp · p 0.42 · regional, not allelic
Overall
CADD	28.6	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 0.044% African / African-American · 33/75,052 alleles

Filtering AF 0.0321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00421% 68/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.044%	2,274
Admixed American	0.0133%	7,503
Remaining individualsnot grpmax-eligible	0.0032%	31,251
South Asian	0.0022%	45,540
European (non-Finnish)	0.00195%	51,306

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.Val1495Met
Coding: c.4483G>A
MANE Select: NM_001271
dbSNP: rs770993927
Type: single nucleotide variant
Location: chr15:93009214 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1495: a UniProt-annotated variant site (in dee94); a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; uncertain significance); the 'chd1 helical c-terminal domain (chct)' 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.Val1495= Likely benign ★★ 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
CHD2 p.Arg1072Ter 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-val1495met (accessed [today's date]).

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