Is RUNX1 p.Pro382= (c.1146G>A) pathogenic?

RUNX1 p.Pro382= (c.1146G>A) is classified Likely benign in RUNX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Very rare (popmax 8.63e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RUNX1 p.Pro382= (c.1146G>A)?

RUNX1 p.Pro382= (c.1146G>A) is associated with Inborn genetic diseases (ClinVar).

How common is RUNX1 p.Pro382= (c.1146G>A) in the general population?

RUNX1 p.Pro382= (c.1146G>A) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

RUNX1 p.Pro382=

c.1146G>A · VCV3948854

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Conditions

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 -0.36	GERP -5.4, phastCons 0.03
Overall
CADD	12.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,159,210 alleles

Overall 7.04e-05% 1/1,420,604 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: RUNX1
Protein: p.Pro382=
Coding: c.1146G>A
MANE Select: NM_001754
Type: single nucleotide variant
Location: chr21:34792432 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.29 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 5 PDB
Residue 382: the 'interaction with foxp3' region; the 'interaction with kat6b' region

Full RUNX1 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

Similar variants

RUNX1 p.Pro382Arg Uncertain significance ★★★ ⚠ same residue
RUNX1 p.Pro382Leu Uncertain significance ★★★ ⚠ same residue
RUNX1 c.508+2T>A Likely pathogenic ★ same condition
RUNX1 c.509-2A>G Likely pathogenic ★ same condition
RUNX1 c.805+6T>G Likely pathogenic ★ same condition
RUNX1 p.Gln230Ter Pathogenic ★ same condition
RUNX1 c.351+4C>A Uncertain significance ★ same condition
RUNX1 c.509-3C>T 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/runx1-p-pro382 (accessed [today's date]).

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