Is DAB2IP p.Ala143Val (c.428C>T) pathogenic?

DAB2IP p.Ala143Val (c.428C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely pathogenic (0.6153); Rare (popmax 0.227%, sas).

How common is DAB2IP p.Ala143Val (c.428C>T) in the general population?

DAB2IP p.Ala143Val (c.428C>T) is rare (popmax 0.227%, sas) (gnomAD).

What do computational predictors say about DAB2IP p.Ala143Val (c.428C>T)?

AlphaMissense predicts likely pathogenic (score 0.6153) — an in-silico prediction, not a clinical call.

DAB2IP p.Ala143Val

c.428C>T · rs576059169 · VCV3079908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6153 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.227%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6153	likely pathogenic
REVEL	0.227	benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 105 kb · p 0.0028 · regional, not allelic
Overall
CADD	28.3	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 0.227% South Asian · 207/91,080 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.192%

Overall 0.0155% 250/1,614,174 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.227%	440
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00668%	14,959
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.0028%	35,758

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.Ala143Val
Coding: c.428C>T
MANE Select: NM_001395010
dbSNP: rs576059169
Type: single nucleotide variant
Location: chr9:121757078 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 143: the ph domain

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

Similar variants

DAB2IP p.Ala143Ser Uncertain significance ★ ⚠ same residue
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

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-ala143val (accessed [today's date]).

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