Is DIP2B p.Thr490Ala (c.1468A>G) pathogenic?

DIP2B p.Thr490Ala (c.1468A>G) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: ambiguous (0.3675); Absent from gnomAD v4.1; Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Thr490Ala (c.1468A>G)?

DIP2B p.Thr490Ala (c.1468A>G) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Thr490Ala (c.1468A>G) in the general population?

DIP2B p.Thr490Ala (c.1468A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIP2B p.Thr490Ala (c.1468A>G)?

AlphaMissense predicts ambiguous (score 0.3675) — an in-silico prediction, not a clinical call.

DIP2B p.Thr490Ala

c.1468A>G · VCV3574930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3675 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, FRA12A type

Computational evidence

Protein change
AlphaMissense	0.3675	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -10.02	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DIP2B
Protein: p.Thr490Ala
Coding: c.1468A>G
MANE Select: NM_173602
Type: single nucleotide variant
Location: chr12:50686599 (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-thr490ala (accessed [today's date]).

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