Is DAXX p.Pro44Thr (c.130C>A) pathogenic?

DAXX p.Pro44Thr (c.130C>A) is classified Uncertain significance in DAXX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: likely benign (0.0671); Ultra-rare (popmax 0.0143%, sas).

How common is DAXX p.Pro44Thr (c.130C>A) in the general population?

DAXX p.Pro44Thr (c.130C>A) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about DAXX p.Pro44Thr (c.130C>A)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

DAXX p.Pro44Thr

c.130C>A · rs771529325 · VCV2302731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.91	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 3.7	GERP 0.53, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 3,179 bp · p 0.00014 · regional, not allelic
Overall
CADD	17.85	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 0.0143% South Asian · 13/91,060 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.000806% 13/1,612,356 alleles · ultra-rare

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: DAXX
Protein: p.Pro44Thr
Coding: c.130C>A
MANE Select: NM_001141969
dbSNP: rs771529325
Type: single nucleotide variant
Location: chr6:33321796 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 64.16 · 14 PDB
Residue 44: the 'necessary for interaction with usp7 and atrx' region; the 'disordered' region

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

Similar variants

DAXX c.-56T>C Uncertain significance ★ same type
DAXX c.-63C>T Uncertain significance ★ same type
DAXX c.-66A>G Uncertain significance ★ same type
DAXX p.Ala103Val Uncertain significance ★ ⚠ same type
DAXX p.Ala396Val Uncertain significance ★ ⚠ same type
DAXX p.Ala545Gly Uncertain significance ★ ⚠ same type
DAXX p.Ala79Val Uncertain significance ★ ⚠ same type
DAXX p.Arg115Gln 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/daxx-p-pro44thr (accessed [today's date]).

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