Is RUNX1 p.Ser331= (c.993C>T) pathogenic?

RUNX1 p.Ser331= (c.993C>T) is classified Likely benign in RUNX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RUNX1 p.Ser331= (c.993C>T)?

RUNX1 p.Ser331= (c.993C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RUNX1 p.Ser331= (c.993C>T) in the general population?

RUNX1 p.Ser331= (c.993C>T) is absent from gnomAD v4.1 (gnomAD).

RUNX1 p.Ser331=

c.993C>T · VCV3948838

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,732)

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 -1.1	GERP -5.1
Overall
CADD	6.875	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,599,732). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RUNX1
Protein: p.Ser331=
Coding: c.993C>T
MANE Select: NM_001754
Type: single nucleotide variant
Location: chr21:34792585 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.29 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 5 PDB
Residue 331: the 'interaction with kat6a' 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.Ser331Arg Uncertain significance ★★★ ⚠ same residue
RUNX1 p.Ser331Gly Uncertain significance ★★★ ⚠ same residue
RUNX1 p.Ser331Thr 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

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-ser331 (accessed [today's date]).

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