Is RUNX2 p.Pro110fs (c.329del) pathogenic?

RUNX2 p.Pro110fs (c.329del) is classified Pathogenic in RUNX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). No gnomAD frequency available for this variant.

How common is RUNX2 p.Pro110fs (c.329del) in the general population?

RUNX2 p.Pro110fs (c.329del) is no gnomAD frequency available for this variant (gnomAD).

RUNX2 p.Pro110fs

c.329del · rs1798259380 · VCV870902

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: RUNX2
Protein: p.Pro110fs
Coding: c.329del
MANE Select: NM_001024630
dbSNP: rs1798259380
Type: Deletion
Location: chr6:45422861 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.02 · 4 PDB
Residue 110: the runt domain; a UniProt-annotated variant site (in clcd1; decreased subcellular localization in the nucleus; decreased transactivation activity)

Full RUNX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RUNX2 p.Thr202fs Pathogenic ★★ same type
RUNX2 c.-11_-9del Benign/Likely benign ★★ same type
RUNX2 c.423+1_423+5del Pathogenic ★ same type
RUNX2 c.581-2del Likely pathogenic ★ same type
RUNX2 p.Ala166fs Likely pathogenic ★ same type
RUNX2 p.Arg100fs Likely pathogenic ★ same type
RUNX2 p.Arg228fs Pathogenic ★ same type
RUNX2 p.Arg92fs 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/runx2-p-pro110fs (accessed [today's date]).

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