Is PGAP1 p.Val28= (c.84C>G) pathogenic?

PGAP1 p.Val28= (c.84C>G) is classified Likely benign in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-12). Very rare (popmax 0.00769%, sas); Associated with hereditary spastic paraplegia.

What condition is associated with PGAP1 p.Val28= (c.84C>G)?

PGAP1 p.Val28= (c.84C>G) is associated with hereditary spastic paraplegia (ClinVar).

How common is PGAP1 p.Val28= (c.84C>G) in the general population?

PGAP1 p.Val28= (c.84C>G) is very rare (popmax 0.00769%, sas) (gnomAD).

PGAP1 p.Val28=

c.84C>G · rs144502622 · VCV1344461

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

hereditary spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.68, phastCons 1
Overall
CADD	10.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,078 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000434% 7/1,612,802 alleles · very rare exomes 6/1,460,512 · genomes 1/152,290 · 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: PGAP1
Protein: p.Val28=
Coding: c.84C>G
MANE Select: NM_024989
dbSNP: rs144502622
Type: single nucleotide variant
Location: chr2:196926533 (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

hereditary spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PGAP1 p.Val28Ile Uncertain significance ★ ⚠ same residue
PGAP1 p.Ile725Asn Uncertain significance ★★ ⚠ same condition
PGAP1 p.Lys111Glu Uncertain significance ★★ ⚠ same condition
PGAP1 p.Phe19Leu Uncertain significance ★★ ⚠ same condition
PGAP1 p.Phe451Tyr Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ser798Leu Uncertain significance ★★ ⚠ same condition
PGAP1 c.1862-3C>T Benign ★★ same condition
PGAP1 p.Ala669= Benign ★★ 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-val28 (accessed [today's date]).

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