Is SIX3 p.Pro74del (c.219_221del) pathogenic?

SIX3 p.Pro74del (c.219221del) is classified Uncertain significance in SIX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). No gnomAD frequency available for this variant.

How common is SIX3 p.Pro74del (c.219_221del) in the general population?

SIX3 p.Pro74del (c.219_221del) is no gnomAD frequency available for this variant (gnomAD).

SIX3 p.Pro74del

c.219_221del · rs760462666 · VCV2429429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 0.42, phastCons 1

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: SIX3
Protein: p.Pro74del
Coding: c.219_221del
MANE Select: NM_005413
dbSNP: rs760462666
Type: Deletion
Location: chr2:44942319 (GRCh38)
Gene constraint: LOEUF 0.387 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.38
Residue 74: the 'interaction with tle5' region

Full SIX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SIX3 p.Pro74Arg Uncertain significance ★★ ⚠ same residue
SIX3 p.Ala121fs Pathogenic ★ same type
SIX3 p.Arg135_Ala139del Pathogenic ★ same type
SIX3 p.Cys212fs Likely pathogenic ★ same type
SIX3 p.Gly244fs Pathogenic ★ same type
SIX3 p.Leu148fs Pathogenic ★ same type
SIX3 p.Thr142fs Pathogenic ★ same type
SIX3 p.Ala44_Gly50del Uncertain significance ★ 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/six3-p-pro74del (accessed [today's date]).

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