Is DAXX p.Ala396Val (c.1187C>T) pathogenic?

DAXX p.Ala396Val (c.1187C>T) is classified Uncertain significance in DAXX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.00254%, nfe).

How common is DAXX p.Ala396Val (c.1187C>T) in the general population?

DAXX p.Ala396Val (c.1187C>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about DAXX p.Ala396Val (c.1187C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

DAXX p.Ala396Val

c.1187C>T · VCV3270902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.01	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 6.5	GERP 0.16, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 3,179 bp · p 0.00014 · regional, not allelic
Overall
CADD	23.7	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 0.00254% European (non-Finnish) · 30/1,179,710 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00198% 32/1,613,664 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,324
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Ala396Val
Coding: c.1187C>T
MANE Select: NM_001141969
Type: single nucleotide variant
Location: chr6:33320444 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 64.16 · 14 PDB
Residue 396: the 'interaction with histone h3.3' region; the 'necessary for interaction with usp7' 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.Ala545Gly Uncertain significance ★ ⚠ same type
DAXX p.Ala79Val Uncertain significance ★ ⚠ same type
DAXX p.Arg115Gln Uncertain significance ★ ⚠ same type
DAXX p.Arg203Gln 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-ala396val (accessed [today's date]).

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