Is DIP2B p.His1389= (c.4167C>T) pathogenic?

DIP2B p.His1389= (c.4167C>T) is classified Likely benign in DIP2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-03). Ultra-rare (popmax 0.0494%, sas); Associated with DIP2B-related disorder.

What condition is associated with DIP2B p.His1389= (c.4167C>T)?

DIP2B p.His1389= (c.4167C>T) is associated with DIP2B-related disorder (ClinVar).

How common is DIP2B p.His1389= (c.4167C>T) in the general population?

DIP2B p.His1389= (c.4167C>T) is ultra-rare (popmax 0.0494%, sas) (gnomAD).

DIP2B p.His1389=

c.4167C>T · rs758518613 · VCV3047259

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, sas)

Conditions

DIP2B-related disorder

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 0.57	GERP -0.27, phastCons 1
Overall
CADD	7.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% South Asian · 45/91,024 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00285% 46/1,613,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0494%	2,023
Remaining individualsnot grpmax-eligible	0.0016%	62,496

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.His1389=
Coding: c.4167C>T
MANE Select: NM_173602
dbSNP: rs758518613
Type: single nucleotide variant
Location: chr12:50737101 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.83

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

Disease context

DIP2B-related disorder

Similar variants

DIP2B p.Ala1101Asp Uncertain significance ★ ⚠ same condition
DIP2B p.Ala1208Ser Uncertain significance ★ ⚠ same condition
DIP2B p.Glu172Ala Uncertain significance ★ ⚠ same condition
DIP2B p.Thr1016Asn Uncertain significance ★ ⚠ same condition
DIP2B p.Ala897Pro Uncertain significance ⚠ same condition
DIP2B p.Asp1565Gly Uncertain significance ⚠ same condition
DIP2B p.Ile792Val Conflicting classifications of pathogenicity ⚠ same condition
DIP2B p.Thr746Arg 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/dip2b-p-his1389 (accessed [today's date]).

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