Is DAZAP1 p.Pro198Leu (c.593C>T) pathogenic?

DAZAP1 p.Pro198Leu (c.593C>T) is classified Uncertain significance in DAZAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.0864); Ultra-rare (popmax 0.0329%, mid).

How common is DAZAP1 p.Pro198Leu (c.593C>T) in the general population?

DAZAP1 p.Pro198Leu (c.593C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about DAZAP1 p.Pro198Leu (c.593C>T)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

DAZAP1 p.Pro198Leu

c.593C>T · rs147255663 · VCV3080137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -8.32	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 3.9	GERP 0.17, phastCons 0.98
Regional constraint	o/e 0.78	unconstrained · MANE · 6,046 bp · p 9e-05 · regional, not allelic
Overall
CADD	24.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,076 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00589% 95/1,612,878 alleles · ultra-rare exomes 87/1,460,738 · genomes 8/152,140 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,038
European (non-Finnish)	0.00695%	14,389
East Asian	0.00446%	22,440
African / African-American	0.00401%	24,960
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
Remaining individualsnot grpmax-eligible	0.0032%	31,229
Finnishnot grpmax-eligible	0.00317%	31,553
South Asian	0.0011%	91,078

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: DAZAP1
Protein: p.Pro198Leu
Coding: c.593C>T
MANE Select: NM_018959
dbSNP: rs147255663
Type: single nucleotide variant
Location: chr19:1428888 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.53 · 2 PDB
Residue 198: the 'disordered' region

Full DAZAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAZAP1 p.Pro271= Benign ★★ same type
DAZAP1 p.Ala214Thr Uncertain significance ★ ⚠ same type
DAZAP1 p.Ala242Thr Uncertain significance ★ ⚠ same type
DAZAP1 p.Ala251Gly Uncertain significance ★ ⚠ same type
DAZAP1 p.Ala255Val Uncertain significance ★ ⚠ same type
DAZAP1 p.Ala331Val Uncertain significance ★ ⚠ same type
DAZAP1 p.Ala340Thr Uncertain significance ★ ⚠ same type
DAZAP1 p.Arg88Trp 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/dazap1-p-pro198leu (accessed [today's date]).

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