Is DIP2B p.Arg682Cys (c.2044C>T) pathogenic?

DIP2B p.Arg682Cys (c.2044C>T) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-24). AlphaMissense: likely pathogenic (0.9437); Very rare (popmax 0.00195%, nfe); Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Arg682Cys (c.2044C>T)?

DIP2B p.Arg682Cys (c.2044C>T) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Arg682Cys (c.2044C>T) in the general population?

DIP2B p.Arg682Cys (c.2044C>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about DIP2B p.Arg682Cys (c.2044C>T)?

AlphaMissense predicts likely pathogenic (score 0.9437) — an in-silico prediction, not a clinical call.

DIP2B p.Arg682Cys

c.2044C>T · VCV4277518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9437 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, FRA12A type

Computational evidence

Protein change
AlphaMissense	0.9437	likely pathogenic
REVEL	0.35	indeterminate
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,802 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00164% 24/1,461,522 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,296
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Arg682Cys
Coding: c.2044C>T
MANE Select: NM_173602
Type: single nucleotide variant
Location: chr12:50697171 (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-arg682cys (accessed [today's date]).

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