Is DIP2B p.Ser245fs (c.732dup) pathogenic?

DIP2B p.Ser245fs (c.732dup) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-21). Very rare (popmax 0.000763%, nfe).

How common is DIP2B p.Ser245fs (c.732dup) in the general population?

DIP2B p.Ser245fs (c.732dup) is very rare (popmax 0.000763%, nfe) (gnomAD).

DIP2B p.Ser245fs

c.732dup · VCV4916773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

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 6 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,024 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,148 alleles · very rare exomes 9/1,461,876 · genomes 0/152,272 · joint denominator

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: DIP2B
Protein: p.Ser245fs
Coding: c.732dup
MANE Select: NM_173602
Type: Duplication
Location: chr12:50674559 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83
Residue 245: the 'disordered' region

Full DIP2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIP2B p.Ser245= Likely benign ★ same residue
DIP2B p.Val297fs Uncertain significance ★★ same type
DIP2B p.Met1009fs 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/dip2b-p-ser245fs (accessed [today's date]).

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