Is PGBD3 p.Ala62= (c.186G>A) pathogenic?

PGBD3 p.Ala62= (c.186G>A) is classified Likely benign in PGBD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-09). Ultra-rare (popmax 0.0657%, mid); Associated with PGBD3-related disorder.

What condition is associated with PGBD3 p.Ala62= (c.186G>A)?

PGBD3 p.Ala62= (c.186G>A) is associated with PGBD3-related disorder (ClinVar).

How common is PGBD3 p.Ala62= (c.186G>A) in the general population?

PGBD3 p.Ala62= (c.186G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

PGBD3 p.Ala62=

c.186G>A · rs201468099 · VCV3053001

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

PGBD3-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 -0.84	GERP -1
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00428% 69/1,613,908 alleles · ultra-rare exomes 67/1,461,808 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
South Asian	0.0483%	2,070
African / African-American	0.00801%	12,482
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.000847%	117,998

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: PGBD3
Protein: p.Ala62=
Coding: c.186G>A
dbSNP: rs201468099
Type: single nucleotide variant
Location: chr10:49516929 (GRCh38)
Structure: AlphaFold pLDDT 84.30

Full PGBD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PGBD3-related disorder

Similar variants

ERCC6 p.Gln534Ter Likely pathogenic ★ same condition
ERCC6 p.Ala434Thr Uncertain significance ★ ⚠ same type
ERCC6 p.Gly443Glu Uncertain significance ★ ⚠ same type
PGBD3 p.Gln98Ter Uncertain significance ★ same type
PGBD3 p.His583Pro Uncertain significance ★ ⚠ same type
PGBD3 p.Leu148His Uncertain significance ★ ⚠ same type
PGBD3 p.Thr34Ala Uncertain significance ★ ⚠ same type
PGBD3 p.Val520Ile 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/pgbd3-p-ala62 (accessed [today's date]).

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