Is CHD3 p.Pro1822Gln (c.5465C>A) pathogenic?

CHD3 p.Pro1822Gln (c.5465C>A) is classified Uncertain significance in CHD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-10). AlphaMissense: likely benign (0.1965); Absent from gnomAD v4.1.

How common is CHD3 p.Pro1822Gln (c.5465C>A) in the general population?

CHD3 p.Pro1822Gln (c.5465C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHD3 p.Pro1822Gln (c.5465C>A)?

AlphaMissense predicts likely benign (score 0.1965) — an in-silico prediction, not a clinical call.

CHD3 p.Pro1822Gln

c.5465C>A · rs752113004 · VCV1312955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1965	likely benign
REVEL	0.738	pathogenic-leaning
SaProt	LLR -6.33	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 1,771 bp · p 3.3e-13 · regional, not allelic
Overall
CADD	28.5	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.Pro1822Gln
Coding: c.5465C>A
MANE Select: NM_001005273
dbSNP: rs752113004
Type: single nucleotide variant
Location: chr17:7909213 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1822: 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.Pro1822Leu Uncertain significance ★ ⚠ 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-pro1822gln (accessed [today's date]).

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