Is DIP2B p.Lys1303Arg (c.3908A>G) pathogenic?

DIP2B p.Lys1303Arg (c.3908A>G) is classified Uncertain significance in DIP2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-26). AlphaMissense: likely benign (0.0722); Very rare (popmax 0.00267%, afr); Associated with intellectual disability, FRA12A type.

What condition is associated with DIP2B p.Lys1303Arg (c.3908A>G)?

DIP2B p.Lys1303Arg (c.3908A>G) is associated with intellectual disability, FRA12A type (ClinVar).

How common is DIP2B p.Lys1303Arg (c.3908A>G) in the general population?

DIP2B p.Lys1303Arg (c.3908A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DIP2B p.Lys1303Arg (c.3908A>G)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

DIP2B p.Lys1303Arg

c.3908A>G · rs1477664803 · VCV1342546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, FRA12A type

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -6.77	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 9.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 240 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00267% African / African-American · 2/74,942 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,614,122 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-Americangrpmax	0.00267%	37,471
European (non-Finnish)	8.47e-05%	1,180,048

Remaining individuals 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.Lys1303Arg
Coding: c.3908A>G
MANE Select: NM_173602
dbSNP: rs1477664803
Type: single nucleotide variant
Location: chr12:50732463 (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-lys1303arg (accessed [today's date]).

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