Is CHD3 p.Arg1759Gln (c.5276G>A) pathogenic?

CHD3 p.Arg1759Gln (c.5276G>A) is classified Likely pathogenic in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1.

How common is CHD3 p.Arg1759Gln (c.5276G>A) in the general population?

CHD3 p.Arg1759Gln (c.5276G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Arg1759Gln (c.5276G>A)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

CHD3 p.Arg1759Gln

c.5276G>A · rs2545128121 · VCV1708782

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic ✓ concordant with ClinVar
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -12.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 732 bp · p 4.1e-05 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHD3
Protein: p.Arg1759Gln
Coding: c.5276G>A
MANE Select: NM_001005273
dbSNP: rs2545128121
Type: single nucleotide variant
Location: chr17:7908711 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1759: the 'required for interaction with pcnt' region; a UniProt-annotated variant site (in snibcps)

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

Similar variants

CHD3 p.Arg1759Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CHD3 c.4073-2A>C Likely pathogenic ★★ same type
CHD3 p.Arg103Ter Pathogenic ★★ same type
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Gln Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Pro Pathogenic/Likely pathogenic ★★ same type
CHD3 p.Arg1169Trp 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/chd3-p-arg1759gln (accessed [today's date]).

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