Is PGBD3 p.Val494Phe (c.1480G>T) pathogenic?

PGBD3 p.Val494Phe (c.1480G>T) is classified Uncertain significance in PGBD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: ambiguous (0.4004); Very rare (popmax 0.00314%, nfe).

How common is PGBD3 p.Val494Phe (c.1480G>T) in the general population?

PGBD3 p.Val494Phe (c.1480G>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about PGBD3 p.Val494Phe (c.1480G>T)?

AlphaMissense predicts ambiguous (score 0.4004) — an in-silico prediction, not a clinical call.

PGBD3 p.Val494Phe

c.1480G>T · rs145326258 · VCV3211754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4004 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

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	0.4004	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -6.37	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 0.1	GERP -0.085, phastCons 0.018
Overall
CADD	15.71	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 0.00314% European (non-Finnish) · 37/1,180,004 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00235% 38/1,613,922 alleles · very rare exomes 30/1,461,794 · genomes 8/152,128 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,892
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Val494Phe
Coding: c.1480G>T
dbSNP: rs145326258
Type: single nucleotide variant
Location: chr10:49515635 (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-val494phe (accessed [today's date]).

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