Is CHD2 c.4137+37A>G pathogenic?

CHD2 c.4137+37A>G is classified Likely benign in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-14). Low-frequency (popmax 1.07%, nfe).

How common is CHD2 c.4137+37A>G in the general population?

CHD2 c.4137+37A>G is low-frequency (popmax 1.07%, nfe) (gnomAD).

CHD2 c.4137+37A>G

rs147884853 · VCV1200476

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +37	near-intronic (+37 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP -2.2, phastCons 0.024
Non-coding constraint	Z 0.16	1 kb window · o/e 0.99 · regional · uncalibrated
Overall
CADD	2.166	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% European (non-Finnish) · 12,462/1,166,914 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.876% 13,915/1,588,428 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	7.13%	14
European (non-Finnish)grpmax	1.07%	94
Admixed American	0.991%	101
Remaining individualsnot grpmax-eligible	0.7%	143
Ashkenazi Jewishnot grpmax-eligible	0.45%	222
Middle Eastern	0.336%	298
African / African-American	0.171%	586
Finnishnot grpmax-eligible	0.103%	972
South Asian	0.0817%	1,224
East Asian	0.00224%	44,574

Amish 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
Coding: c.4137+37A>G
MANE Select: NM_001271
dbSNP: rs147884853
Type: single nucleotide variant
Location: chr15:93000677 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81

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

Similar variants

CHD2 c.1153+1G>C Pathogenic ★★ same type
CHD2 c.1809+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD2 c.294+1G>T Likely pathogenic ★★ same type
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same type
CHD2 c.693-1G>A Likely pathogenic ★★ same type
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ ⚠ same type
CHD2 p.Arg1072Ter Pathogenic ★★ same type
CHD2 p.Arg1137Ter Pathogenic/Likely pathogenic ★★ same type

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-c-4137-plus-37a-g (accessed [today's date]).

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