Is DAXX p.Leu28Pro (c.83T>C) pathogenic?

DAXX p.Leu28Pro (c.83T>C) is classified Likely benign in DAXX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.0423); Absent from gnomAD v4.1.

How common is DAXX p.Leu28Pro (c.83T>C) in the general population?

DAXX p.Leu28Pro (c.83T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAXX p.Leu28Pro (c.83T>C)?

AlphaMissense predicts likely benign (score 0.0423) — an in-silico prediction, not a clinical call.

DAXX p.Leu28Pro

c.83T>C · VCV4009435

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0423 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0423	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -5.70	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 2.7	GERP -1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 3,179 bp · p 0.00014 · regional, not allelic
Overall
CADD	14.27	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAXX
Protein: p.Leu28Pro
Coding: c.83T>C
MANE Select: NM_001141969
Type: single nucleotide variant
Location: chr6:33321843 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 64.16 · 14 PDB
Residue 28: 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-leu28pro (accessed [today's date]).

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