Is PGAP3 p.Arg25Pro (c.74G>C) pathogenic?

PGAP3 p.Arg25Pro (c.74G>C) is classified Uncertain significance in PGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-30). AlphaMissense: likely pathogenic (0.6931); Absent from gnomAD v4.1.

How common is PGAP3 p.Arg25Pro (c.74G>C) in the general population?

PGAP3 p.Arg25Pro (c.74G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAP3 p.Arg25Pro (c.74G>C)?

AlphaMissense predicts likely pathogenic (score 0.6931) — an in-silico prediction, not a clinical call.

PGAP3 p.Arg25Pro

c.74G>C · rs2145169348 · VCV1304340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6931	likely pathogenic
REVEL	0.605	indeterminate
SaProt	LLR -15.20	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.63 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PGAP3
Protein: p.Arg25Pro
Coding: c.74G>C
MANE Select: NM_033419
dbSNP: rs2145169348
Type: single nucleotide variant
Location: chr17:39687941 (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

Similar variants

PGAP3 c.558-10G>A Pathogenic/Likely pathogenic ★★ same type
PGAP3 c.694+1G>A Pathogenic ★★ same type
PGAP3 p.Asp305Gly Pathogenic/Likely pathogenic ★★ same type
PGAP3 p.Gln89Ter Pathogenic ★★ same type
PGAP3 p.Glu37Ter Pathogenic ★★ same type
PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
PGAP3 p.His284Tyr Pathogenic/Likely pathogenic ★★ same type
PGAP3 p.Pro105Gln Likely pathogenic ★★ 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/pgap3-p-arg25pro (accessed [today's date]).

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