Is DIP2B p.Pro1334= (c.4002G>T) pathogenic?

DIP2B p.Pro1334= (c.4002G>T) is classified Likely benign in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). Very rare (popmax 0.00102%, nfe).

How common is DIP2B p.Pro1334= (c.4002G>T) in the general population?

DIP2B p.Pro1334= (c.4002G>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

DIP2B p.Pro1334=

c.4002G>T · VCV3339792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 -0.012	GERP -5.2, phastCons 0.04
Overall
CADD	6.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,012 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,966 alleles · very rare

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.Pro1334=
Coding: c.4002G>T
MANE Select: NM_173602
Type: single nucleotide variant
Location: chr12:50734155 (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

Similar variants

DIP2B p.Asp501Val Uncertain significance ★★ ⚠ same type
DIP2B p.Cys1071Ser Uncertain significance ★★ ⚠ same type
DIP2B p.His1027Arg Uncertain significance ★★ ⚠ same type
DIP2B p.Ile681Val Uncertain significance ★★ ⚠ same type
DIP2B p.Ile968Thr Uncertain significance ★★ ⚠ same type
DIP2B p.Ile994Leu Uncertain significance ★★ ⚠ same type
DIP2B p.Pro244Ala Uncertain significance ★★ ⚠ same type
DIP2B p.Pro513Ser 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-pro1334 (accessed [today's date]).

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