Is RUNX1 p.Pro57Ser (c.169C>T) pathogenic?

RUNX1 p.Pro57Ser (c.169C>T) is classified Uncertain significance in RUNX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0835); No allele count reported in gnomAD v4.1 (AN 1,601,410); Associated with Inborn genetic diseases.

What condition is associated with RUNX1 p.Pro57Ser (c.169C>T)?

RUNX1 p.Pro57Ser (c.169C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RUNX1 p.Pro57Ser (c.169C>T) in the general population?

RUNX1 p.Pro57Ser (c.169C>T) is no allele count reported in gnomAD v4.1 (AN 1,601,410) (gnomAD).

What do computational predictors say about RUNX1 p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

RUNX1 p.Pro57Ser

c.169C>T · VCV3948844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,410)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.412	indeterminate
SaProt	LLR -6.40	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 9.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 162 kb · p 0.93 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P30S vs ClinVar P57S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,410). 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.Pro57Ser
Coding: c.169C>T
MANE Select: NM_001754
Type: single nucleotide variant
Location: chr21:34887025 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.29 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 5 PDB

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.Pro57Arg Uncertain significance ★★★ same residue
RUNX1 p.Pro57Leu Uncertain significance ★★★ ⚠ same residue
RUNX1 p.Pro57= Likely benign ★★★ 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-pro57ser (accessed [today's date]).

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