Is DAZAP1 p.Val142Leu (c.424G>T) pathogenic?

DAZAP1 p.Val142Leu (c.424G>T) is classified Uncertain significance in DAZAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 0.004%, afr).

How common is DAZAP1 p.Val142Leu (c.424G>T) in the general population?

DAZAP1 p.Val142Leu (c.424G>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DAZAP1 p.Val142Leu (c.424G>T)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

DAZAP1 p.Val142Leu

c.424G>T · rs747372596 · VCV3080136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic
REVEL	0.319	indeterminate
SaProt	LLR -9.93	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 12	GERP 0.3, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 7,668 bp · p 3.4e-12 · regional, not allelic
Overall
CADD	27.5	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 0.004% African / African-American · 3/74,940 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,614,018 alleles · very rare exomes 1/1,461,780 · genomes 2/152,238 · 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: DAZAP1
Protein: p.Val142Leu
Coding: c.424G>T
MANE Select: NM_018959
dbSNP: rs747372596
Type: single nucleotide variant
Location: chr19:1422357 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.53 · 2 PDB
Residue 142: the rrm 2 domain; a β-strand

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-val142leu (accessed [today's date]).

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