Is CHD2 p.Val175fs (c.522dup) pathogenic?

CHD2 p.Val175fs (c.522dup) is classified Pathogenic in CHD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-05). Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with CHD2 p.Val175fs (c.522dup)?

CHD2 p.Val175fs (c.522dup) is associated with Inborn genetic diseases (ClinVar).

How common is CHD2 p.Val175fs (c.522dup) in the general population?

CHD2 p.Val175fs (c.522dup) is very rare (popmax 0.0011%, sas) (gnomAD).

CHD2 p.Val175fs

c.522dup · rs748694853 · VCV1746211

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,730 alleles

Overall 0.000137% 2/1,459,218 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,730
European (non-Finnish)	8.49e-05%	1,178,475

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.Val175fs
Coding: c.522dup
MANE Select: NM_001271
dbSNP: rs748694853
Type: Duplication
Location: chr15:92937588 (GRCh38)
Gene constraint: LOEUF 0.174 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.81
Residue 175: a UniProt-annotated variant site (in dee94); 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

Similar variants

CHD2 p.Gln1615fs Pathogenic ★ same condition
CHD2 p.Trp314fs Pathogenic ★ same condition
CHD2 p.Val175= Likely benign ★ same residue
CHD2 c.443+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Ala879Val Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg1152Trp Pathogenic/Likely pathogenic ★★ same condition
CHD2 p.Arg1637Ter Pathogenic ★★ same condition
CHD2 p.Arg1679Ter 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-val175fs (accessed [today's date]).

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