Is DXO p.Pro179Ser (c.535C>T) pathogenic?

DXO p.Pro179Ser (c.535C>T) is classified Uncertain significance in DXO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0818); Ultra-rare (popmax 0.0466%, afr).

How common is DXO p.Pro179Ser (c.535C>T) in the general population?

DXO p.Pro179Ser (c.535C>T) is ultra-rare (popmax 0.0466%, afr) (gnomAD).

What do computational predictors say about DXO p.Pro179Ser (c.535C>T)?

AlphaMissense predicts likely benign (score 0.0818) — an in-silico prediction, not a clinical call.

DXO p.Pro179Ser

c.535C>T · VCV4015521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0466%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0818	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -8.83	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 6.7	GERP 0.41, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,795 bp · p 0.43 · regional, not allelic
Overall
CADD	17.36	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 0.0466% African / African-American · 35/75,028 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00229% 37/1,613,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0466%	2,144
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	8.47e-05%	1,180,012

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.Pro179Ser
Coding: c.535C>T
MANE Select: NM_005510
Type: single nucleotide variant
Location: chr6:31970969 (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.Pro179Leu Uncertain significance ★ ⚠ same residue
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

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-pro179ser (accessed [today's date]).

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