Is PGAP2 p.Ala147Val (c.440C>T) pathogenic?

PGAP2 p.Ala147Val (c.440C>T) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-12). AlphaMissense: ambiguous (0.531); Ultra-rare (popmax 0.0379%, eas).

How common is PGAP2 p.Ala147Val (c.440C>T) in the general population?

PGAP2 p.Ala147Val (c.440C>T) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about PGAP2 p.Ala147Val (c.440C>T)?

AlphaMissense predicts ambiguous (score 0.531) — an in-silico prediction, not a clinical call.

PGAP2 p.Ala147Val

c.440C>T · VCV3710395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.531 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Computational evidence

Protein change
AlphaMissense	0.531	ambiguous
REVEL	0.302	indeterminate
SaProt	LLR -9.03	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	30.0	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 A86V vs ClinVar A147V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,888 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00205% 33/1,612,266 alleles · ultra-rare exomes 30/1,460,156 · genomes 3/152,110 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Admixed American	0.00333%	29,998
South Asian	0.0011%	91,070
European (non-Finnish)	0.00102%	98,334

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.Ala147Val
Coding: c.440C>T
MANE Select: NM_014489
Type: single nucleotide variant
Location: chr11:3823974 (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

Similar variants

PGAP2 p.Ala147= Likely benign ★ same residue
PGAP2 p.Ala127Val Likely pathogenic ★★ same type
PGAP2 p.Arg238Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
PGAP2 p.Thr294Met Likely pathogenic ★★ same type
PGAP2 c.602-3C>T Uncertain significance ★★ same type
PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
PGAP2 p.Ala33Thr Uncertain significance ★★ ⚠ same type
PGAP2 p.Arg238Cys 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/pgap2-p-ala147val (accessed [today's date]).

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