Is DAZAP2 p.Pro133Ser (c.397C>T) pathogenic?

DAZAP2 p.Pro133Ser (c.397C>T) is classified Uncertain significance in DAZAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely pathogenic (0.6073); Very rare (popmax 0.00671%, eas).

How common is DAZAP2 p.Pro133Ser (c.397C>T) in the general population?

DAZAP2 p.Pro133Ser (c.397C>T) is very rare (popmax 0.00671%, eas) (gnomAD).

What do computational predictors say about DAZAP2 p.Pro133Ser (c.397C>T)?

AlphaMissense predicts likely pathogenic (score 0.6073) — an in-silico prediction, not a clinical call.

DAZAP2 p.Pro133Ser

c.397C>T · rs1247980992 · VCV2470267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00671%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6073	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 3,547 bp · p 0.0028 · regional, not allelic
Overall
CADD	25.4	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 0.00671% East Asian · 3/44,686 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.00118% 17/1,445,692 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00671%	14,895
Finnishnot grpmax-eligible	0.00314%	31,802
Admixed American	0.00175%	57,058
European (non-Finnish)	0.000939%	106,526

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.Pro133Ser
Coding: c.397C>T
MANE Select: NM_014764
dbSNP: rs1247980992
Type: single nucleotide variant
Location: chr12:51242348 (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 p.Pro133Leu Likely benign ★ ⚠ same residue
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

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-pro133ser (accessed [today's date]).

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