Is PGAP1 p.Val147Ile (c.439G>A) pathogenic?

PGAP1 p.Val147Ile (c.439G>A) is classified Uncertain significance in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.1057); Very rare (popmax 0.0056%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PGAP1 p.Val147Ile (c.439G>A)?

PGAP1 p.Val147Ile (c.439G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP1 p.Val147Ile (c.439G>A) in the general population?

PGAP1 p.Val147Ile (c.439G>A) is very rare (popmax 0.0056%, nfe) (gnomAD).

What do computational predictors say about PGAP1 p.Val147Ile (c.439G>A)?

AlphaMissense predicts likely benign (score 0.1057) — an in-silico prediction, not a clinical call.

PGAP1 p.Val147Ile

c.439G>A · rs62185192 · VCV2323551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0056%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1057	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.27	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	23.8	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 0.0056% European (non-Finnish) · 66/1,179,526 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00412%

Overall 0.00428% 69/1,612,914 alleles · very rare exomes 69/1,460,630 · genomes 0/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0056%	17,872
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00133%	74,964

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: PGAP1
Protein: p.Val147Ile
Coding: c.439G>A
MANE Select: NM_024989
dbSNP: rs62185192
Type: single nucleotide variant
Location: chr2:196916456 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.15

Full PGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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PGAP1 p.Arg803His Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg814Cys Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn129Ser Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn363Asp Uncertain significance ★★ ⚠ same condition
PGAP1 p.His261Tyr Uncertain significance ★★ ⚠ 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/pgap1-p-val147ile (accessed [today's date]).

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