Is CHD3 p.Pro1519Arg (c.4556C>G) pathogenic?

CHD3 p.Pro1519Arg (c.4556C>G) is classified Uncertain significance in CHD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.597); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHD3 p.Pro1519Arg (c.4556C>G)?

CHD3 p.Pro1519Arg (c.4556C>G) is associated with Inborn genetic diseases, Snijders Blok-Campeau syndrome (ClinVar).

How common is CHD3 p.Pro1519Arg (c.4556C>G) in the general population?

CHD3 p.Pro1519Arg (c.4556C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Pro1519Arg (c.4556C>G)?

AlphaMissense predicts likely pathogenic (score 0.597) — an in-silico prediction, not a clinical call.

CHD3 p.Pro1519Arg

c.4556C>G · rs1567868694 · VCV1696545

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.597 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.597	likely pathogenic
REVEL	0.648	pathogenic-leaning
SaProt	LLR -6.84	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,113 bp · p 0.44 · regional, not allelic
Overall
CADD	25.5	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.Pro1519Arg
Coding: c.4556C>G
MANE Select: NM_001005273
dbSNP: rs1567868694
Type: single nucleotide variant
Location: chr17:7906921 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1519: the 'disordered' region; a UniProt-annotated variant site (in snibcps)

Full CHD3 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: Snijders Blok-Campeau syndrome

Similar variants

CHD3 c.4073-2A>C Likely pathogenic ★★ same condition
CHD3 p.Arg103Ter Pathogenic ★★ same condition
CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1121Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Gln Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Pro Pathogenic/Likely pathogenic ★★ same condition
CHD3 p.Arg1169Trp Pathogenic ★★ same condition
CHD3 p.Arg1172Gln Pathogenic/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-pro1519arg (accessed [today's date]).

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