Is DAZAP2 p.Pro128Leu (c.383C>T) pathogenic?

DAZAP2 p.Pro128Leu (c.383C>T) is classified Likely benign in DAZAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely pathogenic (0.9119); Rare (popmax 0.108%, eas).

How common is DAZAP2 p.Pro128Leu (c.383C>T) in the general population?

DAZAP2 p.Pro128Leu (c.383C>T) is rare (popmax 0.108%, eas) (gnomAD).

What do computational predictors say about DAZAP2 p.Pro128Leu (c.383C>T)?

AlphaMissense predicts likely pathogenic (score 0.9119) — an in-silico prediction, not a clinical call.

DAZAP2 p.Pro128Leu

c.383C>T · VCV3270910

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9119 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.108%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9119	likely pathogenic
REVEL	0.465	indeterminate
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 3,547 bp · p 0.0028 · regional, not allelic
Overall
CADD	25.1	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 0.108% East Asian · 48/44,648 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0747%

Overall 0.00566% 90/1,589,994 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.108%	930
South Asian	0.0171%	5,854
Remaining individualsnot grpmax-eligible	0.00651%	15,362
European (non-Finnish)	0.00197%	50,769

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: DAZAP2
Protein: p.Pro128Leu
Coding: c.383C>T
MANE Select: NM_014764
Type: single nucleotide variant
Location: chr12:51242334 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 58.37

Full DAZAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAZAP2 c.*118G>A Uncertain significance ★ same type
DAZAP2 c.*24G>A Uncertain significance ★ same type
DAZAP2 c.*50C>G Uncertain significance ★ same type
DAZAP2 c.*51T>G Uncertain significance ★ same type
DAZAP2 c.*58A>G Uncertain significance ★ same type
DAZAP2 c.*5C>G Uncertain significance ★ same type
DAZAP2 p.Ala79Thr Uncertain significance ★ ⚠ same type
DAZAP2 p.Arg47Gly 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/dazap2-p-pro128leu (accessed [today's date]).

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