Is CHD2 p.Ile1509= (c.4527C>T) pathogenic?

CHD2 p.Ile1509= (c.4527C>T) is classified Benign in CHD2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 5.61%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Ile1509= (c.4527C>T)?

CHD2 p.Ile1509= (c.4527C>T) is associated with Inborn genetic diseases, developmental and epileptic encephalopathy 94 (ClinVar).

CHD2 p.Ile1509=

Q: How common is CHD2 p.Ile1509= (c.4527C>T) in the general population?

CHD2 p.Ile1509= (c.4527C>T) is common (popmax 5.61%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4527C>T · rs34315566 · VCV257711

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.61%, nfe) — too common for a highly-penetrant pathogenic allele

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 -8.6	GERP -3.7
Overall
CADD	1.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.61% European (non-Finnish) · 66,158/1,179,990 alleles

Filtering AF 5.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.56%

Overall 5% 80,679/1,614,118 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	14.9%	7
European (non-Finnish)grpmax	5.61%	18
Remaining individualsnot grpmax-eligible	4.13%	24
Admixed American	1.03%	97
Amishnot grpmax-eligible	0.987%	101
South Asian	0.961%	104
African / African-American	0.821%	122
Ashkenazi Jewishnot grpmax-eligible	0.784%	128
Middle Eastern	0.742%	135
East Asian	0.00668%	14,961

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile1509=
Coding: c.4527C>T
MANE Select: NM_001271
dbSNP: rs34315566
Type: single nucleotide variant
Location: chr15:93009258 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 1509: 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.Ile1509fs Pathogenic ★ 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-ile1509 (accessed [today's date]).

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