Is PGAP2 p.Ala290Val (c.869C>T) pathogenic?

PGAP2 p.Ala290Val (c.869C>T) is classified Conflicting classifications of pathogenicity in PGAP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.6689); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Ala290Val (c.869C>T)?

PGAP2 p.Ala290Val (c.869C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Ala290Val (c.869C>T) in the general population?

PGAP2 p.Ala290Val (c.869C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about PGAP2 p.Ala290Val (c.869C>T)?

AlphaMissense predicts likely pathogenic (score 0.6689) — an in-silico prediction, not a clinical call.

PGAP2 p.Ala290Val

c.869C>T · rs753497329 · VCV522123

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6689	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A229V vs ClinVar A290V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,064 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00093% 15/1,613,574 alleles · very rare exomes 14/1,461,446 · genomes 1/152,128 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,766
European (non-Finnish)	0.000932%	107,249

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: PGAP2
Protein: p.Ala290Val
Coding: c.869C>T
MANE Select: NM_014489
dbSNP: rs753497329
Type: single nucleotide variant
Location: chr11:3825379 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00

Full PGAP2 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

PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same condition
PGAP2 p.Ala33Thr Uncertain significance ★★ ⚠ same condition
PGAP2 p.Arg238Cys Uncertain significance ★★ ⚠ same condition
PGAP2 p.Glu204Lys Uncertain significance ★★ ⚠ same condition
PGAP2 p.Leu161Phe Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val183Met Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val4Ile Uncertain significance ★★ ⚠ same condition
PGAP2 p.Val182Ile Benign/Likely 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/pgap2-p-ala290val (accessed [today's date]).

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