Is DAXX p.Arg203Trp (c.607C>T) pathogenic?

DAXX p.Arg203Trp (c.607C>T) is classified Uncertain significance in DAXX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.1595); Ultra-rare (popmax 0.0165%, mid).

How common is DAXX p.Arg203Trp (c.607C>T) in the general population?

DAXX p.Arg203Trp (c.607C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DAXX p.Arg203Trp (c.607C>T)?

AlphaMissense predicts likely benign (score 0.1595) — an in-silico prediction, not a clinical call.

DAXX p.Arg203Trp

c.607C>T · rs746835251 · VCV3080131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1595 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1595	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -14.57	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.88, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 3,179 bp · p 0.00014 · regional, not allelic
Overall
CADD	25.7	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00062% 10/1,613,638 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
East Asian	0.00668%	14,960
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000424%	235,919

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.Arg203Trp
Coding: c.607C>T
MANE Select: NM_001141969
dbSNP: rs746835251
Type: single nucleotide variant
Location: chr6:33321168 (GRCh38)
Gene constraint: LOEUF 0.524 · pLI 0.89 (gnomAD)
Structure: AlphaFold pLDDT 64.16 · 14 PDB
Residue 203: the 'interaction with histone h3.3' region; an α-helix

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

Similar variants

DAXX p.Arg203Gln Uncertain significance ★ ⚠ same residue
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

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-arg203trp (accessed [today's date]).

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