Is PGAP1 p.Gly85Val (c.254G>T) pathogenic?

PGAP1 p.Gly85Val (c.254G>T) is classified Uncertain significance in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1.

How common is PGAP1 p.Gly85Val (c.254G>T) in the general population?

PGAP1 p.Gly85Val (c.254G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAP1 p.Gly85Val (c.254G>T)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

PGAP1 p.Gly85Val

c.254G>T · VCV4959304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic · top 4% in PGAP1
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -16.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	28.4	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: PGAP1
Protein: p.Gly85Val
Coding: c.254G>T
MANE Select: NM_024989
Type: single nucleotide variant
Location: chr2:196920044 (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

Similar variants

PGAP1 p.Arg231Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Gln466Ter Pathogenic ★★ same type
PGAP1 p.Gln555Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Tyr758Ter Pathogenic/Likely pathogenic ★★ same type
PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same type
PGAP1 p.Ala714Val Uncertain significance ★★ ⚠ same type
PGAP1 p.Ala864Val Uncertain significance ★★ ⚠ same type
PGAP1 p.Arg231Gln Uncertain significance ★★ ⚠ 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/pgap1-p-gly85val (accessed [today's date]).

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