Is PML p.Asp179= (c.537C>T) pathogenic?

PML p.Asp179= (c.537C>T) is classified Likely benign in PML (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-14). Ultra-rare (popmax 0.0107%, afr); Associated with PML-related disorder.

What condition is associated with PML p.Asp179= (c.537C>T)?

PML p.Asp179= (c.537C>T) is associated with PML-related disorder (ClinVar).

How common is PML p.Asp179= (c.537C>T) in the general population?

PML p.Asp179= (c.537C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

PML p.Asp179=

c.537C>T · rs780737061 · VCV3051387

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

PML-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.3
Overall
CADD	3.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,920 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00112% 18/1,613,850 alleles · ultra-rare exomes 9/1,461,668 · genomes 9/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,365
East Asian	0.00668%	14,959
Remaining individualsnot grpmax-eligible	0.0032%	31,237
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,086
European (non-Finnish)	0.000254%	393,295

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: PML
Protein: p.Asp179=
Coding: c.537C>T
MANE Select: NM_033238
dbSNP: rs780737061
Type: single nucleotide variant
Location: chr15:73998411 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 71.17 · 20 PDB

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

Disease context

PML-related disorder

Similar variants

PML c.1710+1152C>T Uncertain significance ★ same condition
PML c.1710+98G>A Uncertain significance ★ same condition
PML p.Val345Met Uncertain significance ★ ⚠ same condition
PML c.1710+1029G>A Likely benign same condition
PML c.1710+1335G>C Likely benign same condition
PML c.1710+1467G>A Likely benign same condition
PML c.1710+685C>T Likely benign same condition
PML c.1710+833C>T Likely benign same condition

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/pml-p-asp179 (accessed [today's date]).

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