Is DAB1 p.Pro328Ser (c.982C>T) pathogenic?

DAB1 p.Pro328Ser (c.982C>T) is classified Uncertain significance in DAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.0625); Ultra-rare (popmax 0.0165%, mid).

How common is DAB1 p.Pro328Ser (c.982C>T) in the general population?

DAB1 p.Pro328Ser (c.982C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DAB1 p.Pro328Ser (c.982C>T)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

DAB1 p.Pro328Ser

c.982C>T · rs561439816 · VCV2272952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.56	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 5.1	GERP -0.65, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	22.5	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 P361S vs ClinVar P328S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000248% 4/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0022%	45,534
European (non-Finnish)	8.47e-05%	1,180,038

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.Pro328Ser
Coding: c.982C>T
MANE Select: NM_001365792
dbSNP: rs561439816
Type: single nucleotide variant
Location: chr1:57015345 (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-pro328ser (accessed [today's date]).

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