Is DXO p.Asp55Glu (c.165T>G) pathogenic?

DXO p.Asp55Glu (c.165T>G) is classified Uncertain significance in DXO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.8822); Ultra-rare (popmax 0.0309%, nfe).

How common is DXO p.Asp55Glu (c.165T>G) in the general population?

DXO p.Asp55Glu (c.165T>G) is ultra-rare (popmax 0.0309%, nfe) (gnomAD).

What do computational predictors say about DXO p.Asp55Glu (c.165T>G)?

AlphaMissense predicts likely pathogenic (score 0.8822) — an in-silico prediction, not a clinical call.

DXO p.Asp55Glu

c.165T>G · rs199557774 · VCV2217220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8822	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -12.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -2.3, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 1,795 bp · p 0.43 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0309% European (non-Finnish) · 365/1,180,040 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0234% 378/1,614,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0309%	3,233
Remaining individualsnot grpmax-eligible	0.016%	6,251
African / African-American	0.004%	25,011

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: DXO
Protein: p.Asp55Glu
Coding: c.165T>G
MANE Select: NM_005510
dbSNP: rs199557774
Type: single nucleotide variant
Location: chr6:31971511 (GRCh38)
Gene constraint: LOEUF 1.264 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.96

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

Similar variants

DXO p.Ala338Thr Uncertain significance ★ ⚠ same type
DXO p.Ala372Thr Uncertain significance ★ ⚠ same type
DXO p.Ala64Asp Uncertain significance ★ ⚠ same type
DXO p.Arg145Gln Uncertain significance ★ ⚠ same type
DXO p.Arg155Gly Uncertain significance ★ ⚠ same type
DXO p.Arg177Gln Uncertain significance ★ ⚠ same type
DXO p.Arg177Trp Uncertain significance ★ ⚠ same type
DXO p.Arg221Cys 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/dxo-p-asp55glu (accessed [today's date]).

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