CHD7 p.Leu1322Pro
c.3965T>C · VCV3766397
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9998 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
AlphaMissense, REVEL · SaProt no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9998 | likely pathogenic ✓ concordant with ClinVar · top 2% in CHD7 |
|---|---|---|
| REVEL | 0.991 | strongly pathogenic-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.55 | unconstrained · MANE · 14 kb · p 1.9e-20 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
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
- CHD7
- Protein
- p.Leu1322Pro
- Coding
- c.3965T>C
- MANE Select
- NM_017780
- Type
- single nucleotide variant
- Location
- chr8:60836259 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 1322
- a UniProt-annotated variant site (in charges; uncertain significance); the helicase c-terminal domain
Similar variants
- CHD7 p.Leu1322Val Uncertain significance ★ same residue
- CHD7 p.Leu1322fs Pathogenic ★ same residue
- CHD7 c.2097-2A>G Pathogenic ★★ same type
- CHD7 c.2238+1G>A Pathogenic ★★ same type
- CHD7 c.2377-1G>A Likely pathogenic ★★ same type
- CHD7 c.2613+1G>A Pathogenic/Likely pathogenic ★★ same type
- CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same type
- CHD7 c.2836-2A>T 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/chd7-p-leu1322pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown