Is PGBD3 p.Ala62Val (c.185C>T) pathogenic?

PGBD3 p.Ala62Val (c.185C>T) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-19). AlphaMissense: ambiguous (0.3942); Very rare (popmax 0.00167%, amr).

How common is PGBD3 p.Ala62Val (c.185C>T) in the general population?

PGBD3 p.Ala62Val (c.185C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PGBD3 p.Ala62Val (c.185C>T)?

AlphaMissense predicts ambiguous (score 0.3942) — an in-silico prediction, not a clinical call.

PGBD3 p.Ala62Val

c.185C>T · VCV3931183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3942	ambiguous
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.17	GERP -0.39
Overall
CADD	10.91	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 0.00167% Admixed American · 1/59,990 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,940 alleles · very rare exomes 3/1,461,810 · genomes 1/152,130 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,990
African / African-American	0.00134%	74,906
European (non-Finnish)	0.000169%	589,988

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.Ala62Val
Coding: c.185C>T
Type: single nucleotide variant
Location: chr10:49516930 (GRCh38)

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

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-ala62val (accessed [today's date]).

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