Is DAB2IP p.Pro72Leu (c.215C>T) pathogenic?

DAB2IP p.Pro72Leu (c.215C>T) is classified Uncertain significance in DAB2IP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.7911); Very rare (popmax 0.00451%, sas).

How common is DAB2IP p.Pro72Leu (c.215C>T) in the general population?

DAB2IP p.Pro72Leu (c.215C>T) is very rare (popmax 0.00451%, sas) (gnomAD).

What do computational predictors say about DAB2IP p.Pro72Leu (c.215C>T)?

AlphaMissense predicts likely pathogenic (score 0.7911) — an in-silico prediction, not a clinical call.

DAB2IP p.Pro72Leu

c.215C>T · VCV3499526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7911	likely pathogenic
REVEL	0.253	benign-leaning
SaProt	LLR -6.24	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.19	unconstrained · MANE · 105 kb · p 0.0028 · regional, not allelic
Overall
CADD	26.1	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 0.00451% South Asian · 4/88,680 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00091%

Overall 0.000878% 14/1,593,642 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00451%	22,170
Remaining individualsnot grpmax-eligible	0.00325%	30,734
Admixed American	0.00171%	58,534
European (non-Finnish)	0.000599%	167,063

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.Pro72Leu
Coding: c.215C>T
MANE Select: NM_001395010
Type: single nucleotide variant
Location: chr9:121678768 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.74
Residue 72: the 'disordered' region

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-pro72leu (accessed [today's date]).

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