Is DAB1 p.Leu346Pro (c.1037T>C) pathogenic?

DAB1 p.Leu346Pro (c.1037T>C) is classified Uncertain significance in DAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely benign (0.265); Ultra-rare (popmax 0.0317%, amr).

How common is DAB1 p.Leu346Pro (c.1037T>C) in the general population?

DAB1 p.Leu346Pro (c.1037T>C) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about DAB1 p.Leu346Pro (c.1037T>C)?

AlphaMissense predicts likely benign (score 0.265) — an in-silico prediction, not a clinical call.

DAB1 p.Leu346Pro

c.1037T>C · VCV3270767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.265 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.265	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.39	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	28.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L379P vs ClinVar L346P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/60,008 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00477% 77/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
Middle Eastern	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,801
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	0.00407%	24,584
African / African-American	0.004%	24,971

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: DAB1
Protein: p.Leu346Pro
Coding: c.1037T>C
MANE Select: NM_001365792
Type: single nucleotide variant
Location: chr1:57015290 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.20

Full DAB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAB1 p.Ala103Val Uncertain significance ★★ ⚠ same type
DAB1 p.Ala75Thr Uncertain significance ★★ ⚠ same type
DAB1 p.Arg41Gln Uncertain significance ★★ ⚠ same type
DAB1 p.Pro334Leu Uncertain significance ★★ ⚠ same type
DAB1 p.Pro376Ala Uncertain significance ★★ ⚠ same type
DAB1 p.Pro391Ser Uncertain significance ★★ ⚠ same type
DAB1 p.Pro516Leu Uncertain significance ★★ ⚠ same type
DAB1 p.Val240Leu Uncertain significance ★★ ⚠ 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/dab1-p-leu346pro (accessed [today's date]).

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