Is DAB2IP p.Arg198Trp (c.592C>T) pathogenic?

DAB2IP p.Arg198Trp (c.592C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely pathogenic (0.7736); Very rare (popmax 0.00891%, eas).

How common is DAB2IP p.Arg198Trp (c.592C>T) in the general population?

DAB2IP p.Arg198Trp (c.592C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DAB2IP p.Arg198Trp (c.592C>T)?

AlphaMissense predicts likely pathogenic (score 0.7736) — an in-silico prediction, not a clinical call.

DAB2IP p.Arg198Trp

c.592C>T · VCV3270786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7736	likely pathogenic
REVEL	0.791	moderately pathogenic-leaning
SaProt	LLR -13.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.74, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 16 kb · p 2.6e-17 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00891% East Asian · 4/44,870 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00192% 28/1,460,796 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,218
Admixed American	0.00334%	29,958
Remaining individualsnot grpmax-eligible	0.0032%	31,237
South Asian	0.00221%	45,231
European (non-Finnish)	0.00153%	65,546

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: DAB2IP
Protein: p.Arg198Trp
Coding: c.592C>T
MANE Select: NM_001395010
Type: single nucleotide variant
Location: chr9:121758973 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 198: the ph domain; the c2 domain

Full DAB2IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB2IP p.Ala816Thr Benign ★★ same type
DAB2IP p.Arg199= Benign ★★ same type
DAB2IP p.Arg966His Benign ★★ same type
DAB2IP p.Asp97= Benign/Likely benign ★★ same type
DAB2IP p.Lys284= Benign ★★ same type
DAB2IP p.Pro126= Likely benign ★★ same type
DAB2IP p.Ser460Leu Benign ★★ ⚠ same type
DAB2IP p.Ser68= Likely 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/dab2ip-p-arg198trp (accessed [today's date]).

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