Is CHD3 p.Pro1922Leu (c.5765C>T) pathogenic?

CHD3 p.Pro1922Leu (c.5765C>T) is classified Likely benign in CHD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-16). AlphaMissense: likely benign (0.1272); Ultra-rare (popmax 0.0112%, eas); Associated with CHD3-related disorder.

What condition is associated with CHD3 p.Pro1922Leu (c.5765C>T)?

CHD3 p.Pro1922Leu (c.5765C>T) is associated with CHD3-related disorder (ClinVar).

How common is CHD3 p.Pro1922Leu (c.5765C>T) in the general population?

CHD3 p.Pro1922Leu (c.5765C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about CHD3 p.Pro1922Leu (c.5765C>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

CHD3 p.Pro1922Leu

c.5765C>T · rs201169642 · VCV3036533

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CHD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,019 bp · p 0.084 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.0112% East Asian · 5/44,792 alleles

Filtering AF 0.00522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00391%

Overall 0.00306% 49/1,602,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,958
South Asian	0.0101%	9,948
Admixed American	0.00536%	18,663
African / African-American	0.0027%	37,018
European (non-Finnish)	0.00255%	39,207

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: CHD3
Protein: p.Pro1922Leu
Coding: c.5765C>T
MANE Select: NM_001005273
dbSNP: rs201169642
Type: single nucleotide variant
Location: chr17:7910857 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.21
Residue 1922: 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

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.Met1085Ile Likely pathogenic ★ same condition
CHD3 p.Ala1289Thr Conflicting classifications of pathogenicity ★ ⚠ 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-pro1922leu (accessed [today's date]).

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