Is PGAP3 p.Pro134Ala (c.400C>G) pathogenic?

PGAP3 p.Pro134Ala (c.400C>G) is classified Uncertain significance in PGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.2211); Very rare (popmax 0.000124%); Associated with Inborn genetic diseases.

What condition is associated with PGAP3 p.Pro134Ala (c.400C>G)?

PGAP3 p.Pro134Ala (c.400C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP3 p.Pro134Ala (c.400C>G) in the general population?

PGAP3 p.Pro134Ala (c.400C>G) is very rare (popmax 0.000124%) (gnomAD).

What do computational predictors say about PGAP3 p.Pro134Ala (c.400C>G)?

AlphaMissense predicts likely benign (score 0.2211) — an in-silico prediction, not a clinical call.

PGAP3 p.Pro134Ala

c.400C>G · rs2543804138 · VCV2329887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2211 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000124%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2211	likely benign
REVEL	0.539	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.63 · regional, not allelic
Overall
CADD	26.5	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 0.000124%

Overall 0.000124% 2/1,614,060 alleles · very rare exomes 2/1,461,670 · genomes 0/152,390 · joint denominator

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: PGAP3
Protein: p.Pro134Ala
Coding: c.400C>G
MANE Select: NM_033419
dbSNP: rs2543804138
Type: single nucleotide variant
Location: chr17:39684629 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.17

Full PGAP3 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

PGAP3 p.Pro134Leu Uncertain significance ★ same residue
PGAP3 p.Glu37Ter Pathogenic ★★ same condition
PGAP3 p.Arg126Cys Uncertain significance ★★ ⚠ same condition
PGAP3 p.Gly84Asp Uncertain significance ★★ ⚠ same condition
PGAP3 p.Thr161Ile Uncertain significance ★★ same condition
PGAP3 p.Val145Ala Uncertain significance ★★ same condition
PGAP3 p.Val211Asp Uncertain significance ★★ ⚠ same condition
PGAP3 p.Val253Met 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/pgap3-p-pro134ala (accessed [today's date]).

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