Is DIP2B p.Pro1384= (c.4152G>A) pathogenic?

DIP2B p.Pro1384= (c.4152G>A) is classified Benign/Likely benign in DIP2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-30). Low-frequency (popmax 1.58%, sas); Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Pro1384= (c.4152G>A)?

DIP2B p.Pro1384= (c.4152G>A) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Pro1384= (c.4152G>A) in the general population?

DIP2B p.Pro1384= (c.4152G>A) is low-frequency (popmax 1.58%, sas) (gnomAD).

DIP2B p.Pro1384=

c.4152G>A · rs141436517 · VCV1255503

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.58%, sas)

Conditions

intellectual disability, FRA12A type

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 -0.93	GERP -5, phastCons 0.007
Overall
CADD	7.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.58% South Asian · 1,442/91,054 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.49%

Overall 0.273% 4,413/1,613,930 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.3%	43
South Asiangrpmax	1.58%	63
Middle Eastern	1.22%	82
Remaining individualsnot grpmax-eligible	0.323%	309
Admixed American	0.287%	349
European (non-Finnish)	0.199%	502
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Finnishnot grpmax-eligible	0.116%	865
African / African-American	0.0387%	2,587

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1384=
Coding: c.4152G>A
MANE Select: NM_173602
dbSNP: rs141436517
Type: single nucleotide variant
Location: chr12:50737086 (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

intellectual disability, FRA12A type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIP2B p.Pro1384Leu Uncertain significance ★ ⚠ same residue
DIP2B p.Asp501Val Uncertain significance ★★ ⚠ same condition
DIP2B p.Pro513Ser Uncertain significance ★★ ⚠ same condition
DIP2B p.Val584Ile Uncertain significance ★★ ⚠ same condition
DIP2B c.1814-15T>C Benign ★★ same condition
DIP2B c.4355-32A>G Benign ★★ same condition
DIP2B p.Asn982= Benign ★★ same condition
DIP2B p.Ile1477= Benign ★★ 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-pro1384 (accessed [today's date]).

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