Is DIP2B p.Pro802Leu (c.2405C>T) pathogenic?

DIP2B p.Pro802Leu (c.2405C>T) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely pathogenic (0.8871); Very rare (popmax 0.00111%, sas); Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Pro802Leu (c.2405C>T)?

DIP2B p.Pro802Leu (c.2405C>T) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Pro802Leu (c.2405C>T) in the general population?

DIP2B p.Pro802Leu (c.2405C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about DIP2B p.Pro802Leu (c.2405C>T)?

AlphaMissense predicts likely pathogenic (score 0.8871) — an in-silico prediction, not a clinical call.

DIP2B p.Pro802Leu

c.2405C>T · rs2139565009 · VCV2688933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, FRA12A type

Computational evidence

Protein change
AlphaMissense	0.8871	likely pathogenic
REVEL	0.377	indeterminate
SaProt	LLR -10.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/89,740 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000275% 4/1,456,476 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	89,740
European (non-Finnish)	0.000255%	392,898

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.Pro802Leu
Coding: c.2405C>T
MANE Select: NM_173602
dbSNP: rs2139565009
Type: single nucleotide variant
Location: chr12:50704219 (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.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
DIP2B p.Pro1384= Benign/Likely 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-pro802leu (accessed [today's date]).

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