SMAD2 p.Pro377=
c.1131A>C · rs2511313829 · VCV2566857
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.96 | GERP 0.77, phastCons 1 |
| Overall | ||
| CADD | 10.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,868 alleles
Overall
6.84e-05%
1/1,461,680 alleles · very rare
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
- SMAD2
- Protein
- p.Pro377=
- Coding
- c.1131A>C
- MANE Select
- NM_005901
- dbSNP
- rs2511313829
- Type
- single nucleotide variant
- Location
- chr18:47845667 (GRCh38)
- Gene constraint
- LOEUF 0.249 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50 · 10 PDB
- Residue 377
- a UniProt-annotated variant site (in chtd8); the mh2 domain
Similar variants
- SMAD2 p.Ala395Ser Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Asn307Asp Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Asn318Ser Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Asn361Ser Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Asn91Asp Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Cys81Phe Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Gln236His Uncertain significance ★★ ⚠ same condition
- SMAD2 p.Ile127Met Uncertain significance ★★ ⚠ 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/smad2-p-pro377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown