Is DAB1 p.Pro386Arg (c.1157C>G) pathogenic?

DAB1 p.Pro386Arg (c.1157C>G) is classified Uncertain significance in DAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.2545); Very rare (popmax 0.000424%, nfe).

How common is DAB1 p.Pro386Arg (c.1157C>G) in the general population?

DAB1 p.Pro386Arg (c.1157C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about DAB1 p.Pro386Arg (c.1157C>G)?

AlphaMissense predicts likely benign (score 0.2545) — an in-silico prediction, not a clinical call.

DAB1 p.Pro386Arg

c.1157C>G · VCV4237317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2545	likely benign
REVEL	0.367	indeterminate
SaProt	LLR -10.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P419R vs ClinVar P386R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,014 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,020 alleles · very rare exomes 4/1,461,838 · genomes 1/152,182 · joint denominator

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.Pro386Arg
Coding: c.1157C>G
MANE Select: NM_001365792
Type: single nucleotide variant
Location: chr1:57015170 (GRCh38)
Gene constraint: LOEUF 0.407 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.20
Residue 419 UniProt numbering: the 'disordered' region

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

Similar variants

DAB1 p.Pro386Ser Uncertain significance ★ ⚠ same residue
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

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-pro386arg (accessed [today's date]).

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