Is DIP2B p.Arg484Trp (c.1450C>T) pathogenic?

DIP2B p.Arg484Trp (c.1450C>T) is classified Benign in DIP2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely benign (0.2611); Low-frequency (popmax 2.34%, nfe); Associated with DIP2B-related disorder.

What condition is associated with DIP2B p.Arg484Trp (c.1450C>T)?

DIP2B p.Arg484Trp (c.1450C>T) is associated with DIP2B-related disorder (ClinVar).

How common is DIP2B p.Arg484Trp (c.1450C>T) in the general population?

DIP2B p.Arg484Trp (c.1450C>T) is low-frequency (popmax 2.34%, nfe) (gnomAD).

What do computational predictors say about DIP2B p.Arg484Trp (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.2611) — an in-silico prediction, not a clinical call.

DIP2B p.Arg484Trp

c.1450C>T · rs74751916 · VCV3037939

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2611 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.34%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIP2B-related disorder

Computational evidence

Protein change
AlphaMissense	0.2611	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	27.4	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 2.34% European (non-Finnish) · 27,615/1,179,860 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.31%

Overall 2.07% 33,405/1,613,748 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.44%	23
European (non-Finnish)grpmax	2.34%	43
Ashkenazi Jewishnot grpmax-eligible	1.8%	56
Remaining individualsnot grpmax-eligible	1.72%	58
Admixed American	0.929%	108
Middle Eastern	0.512%	195
South Asian	0.508%	197
Amishnot grpmax-eligible	0.44%	228
African / African-American	0.377%	265
East Asian	0.00892%	11,216

Finnish 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.Arg484Trp
Coding: c.1450C>T
MANE Select: NM_173602
dbSNP: rs74751916
Type: single nucleotide variant
Location: chr12:50686581 (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

DIP2B-related disorder

Similar variants

DIP2B p.Ala1101Asp Uncertain significance ★ ⚠ same condition
DIP2B p.Ala1208Ser Uncertain significance ★ ⚠ same condition
DIP2B p.Glu172Ala Uncertain significance ★ ⚠ same condition
DIP2B p.Thr1016Asn Uncertain significance ★ ⚠ same condition
DIP2B p.Ala897Pro Uncertain significance ⚠ same condition
DIP2B p.Asp1565Gly Uncertain significance ⚠ same condition
DIP2B p.Ile792Val Conflicting classifications of pathogenicity ⚠ same condition
DIP2B p.Thr746Arg Uncertain significance ⚠ 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-arg484trp (accessed [today's date]).

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