Is DIPK2B p.Arg143Leu (c.428G>T) pathogenic?

DIPK2B p.Arg143Leu (c.428G>T) is classified Benign in DIPK2B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-01). AlphaMissense: likely benign (0.1794); Low-frequency (popmax 2.67%, amr); Associated with DIPK2B-related disorder.

What condition is associated with DIPK2B p.Arg143Leu (c.428G>T)?

DIPK2B p.Arg143Leu (c.428G>T) is associated with DIPK2B-related disorder (ClinVar).

How common is DIPK2B p.Arg143Leu (c.428G>T) in the general population?

DIPK2B p.Arg143Leu (c.428G>T) is low-frequency (popmax 2.67%, amr) (gnomAD).

What do computational predictors say about DIPK2B p.Arg143Leu (c.428G>T)?

AlphaMissense predicts likely benign (score 0.1794) — an in-silico prediction, not a clinical call.

DIPK2B p.Arg143Leu

c.428G>T · rs144500092 · VCV3033826

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1794 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.67%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DIPK2B-related disorder

Computational evidence

Protein change
AlphaMissense	0.1794	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.54	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 1.3	GERP -1, phastCons 0.76
Regional constraint	o/e 0.99	unconstrained · MANE · 49 kb · p 0.86 · regional, not allelic
Overall
CADD	12.85	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 2.67% Admixed American · 1,227/45,909 alleles

Filtering AF 2.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5%

Overall 0.116% 1,403/1,210,636 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.67%	37
East Asian	0.178%	563
Remaining individualsnot grpmax-eligible	0.128%	781
African / African-American	0.0401%	2,496
South Asian	0.0176%	5,685
European (non-Finnish)	0.00246%	40,695

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: DIPK2B
Protein: p.Arg143Leu
Coding: c.428G>T
MANE Select: NM_176819
dbSNP: rs144500092
Type: single nucleotide variant
Location: chrX:45191821 (GRCh38)
Structure: AlphaFold pLDDT 84.17

Full DIPK2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DIPK2B-related disorder

Similar variants

DIPK2B p.Gly231Arg Uncertain significance ⚠ same condition
DIPK2B p.Arg128Lys Benign same condition
DIPK2B p.Asp391His Likely benign ⚠ same condition
DIPK2B p.Leu366= Likely benign same condition
DIPK2B p.Ser105Pro Benign ⚠ same condition
DIPK2B p.Ser340= Likely benign same condition
DIPK2B p.Ala133Glu Benign ★★ same type
DIPK2B p.Lys364= Benign ★★ same type

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/dipk2b-p-arg143leu (accessed [today's date]).

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