Is CHD3 p.Glu549fs (c.1646_1647del) pathogenic?

CHD3 p.Glu549fs (c.16461647del) is classified Likely pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). Absent from gnomAD; Associated with CHD3-related disorder.

What condition is associated with CHD3 p.Glu549fs (c.1646_1647del)?

CHD3 p.Glu549fs (c.1646_1647del) is associated with CHD3-related disorder (ClinVar).

How common is CHD3 p.Glu549fs (c.1646_1647del) in the general population?

CHD3 p.Glu549fs (c.1646_1647del) is absent from gnomAD (gnomAD).

CHD3 p.Glu549fs

c.1646_1647del · rs2544842904 · VCV2632907

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CHD3-related disorder

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 40
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP 0.74, phastCons 0.99

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHD3
Protein: p.Glu549fs
Coding: c.1646_1647del
MANE Select: NM_001005273
dbSNP: rs2544842904
Type: Microsatellite
Location: chr17:7895478 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 549: the chromo 1 domain; a UniProt-annotated variant site (in snibcps)

Full CHD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CHD3-related disorder

Similar variants

CHD3 p.Arg1172Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1342Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg985Gln Pathogenic ★★ same condition
CHD3 p.Arg1491His Uncertain significance ★★ ⚠ same condition
CHD3 p.Arg684Ter Pathogenic ★ same condition
CHD3 p.Glu1653Ter Likely pathogenic ★ same condition
CHD3 p.Lys1044fs Likely pathogenic ★ same condition
CHD3 p.Met1085Ile 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/chd3-p-glu549fs (accessed [today's date]).

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