Is DAXX p.Arg371Trp (c.1111C>T) pathogenic?

DAXX p.Arg371Trp (c.1111C>T) is classified Uncertain significance in DAXX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: ambiguous (0.4215); Very rare (popmax 0.005%, amr).

How common is DAXX p.Arg371Trp (c.1111C>T) in the general population?

DAXX p.Arg371Trp (c.1111C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DAXX p.Arg371Trp (c.1111C>T)?

AlphaMissense predicts ambiguous (score 0.4215) — an in-silico prediction, not a clinical call.

DAXX p.Arg371Trp

c.1111C>T · VCV3838290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.4215	ambiguous
REVEL	0.388	indeterminate
SaProt	LLR -13.76	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.14, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 3,179 bp · p 0.00014 · regional, not allelic
Overall
CADD	31.0	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 0.005% Admixed American · 3/59,986 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000558% 9/1,613,774 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00134%	74,902
European (non-Finnish)	0.000339%	294,976

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.Arg371Trp
Coding: c.1111C>T
MANE Select: NM_001141969
Type: single nucleotide variant
Location: chr6:33320520 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 64.16 · 14 PDB
Residue 371: an α-helix; the 'interaction with histone h3.3' region; the 'necessary for interaction with usp7' 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-arg371trp (accessed [today's date]).

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