Is PGAP2 p.Pro172Leu (c.515C>T) pathogenic?

PGAP2 p.Pro172Leu (c.515C>T) is classified Likely benign in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely benign (0.0649); Rare (popmax 0.114%, sas); Associated with Inborn genetic diseases.

What condition is associated with PGAP2 p.Pro172Leu (c.515C>T)?

PGAP2 p.Pro172Leu (c.515C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP2 p.Pro172Leu (c.515C>T) in the general population?

PGAP2 p.Pro172Leu (c.515C>T) is rare (popmax 0.114%, sas) (gnomAD).

What do computational predictors say about PGAP2 p.Pro172Leu (c.515C>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

PGAP2 p.Pro172Leu

c.515C>T · VCV3417280

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.18	GERP -2.7, phastCons 0.006
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	9.078	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 P111L vs ClinVar P172L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.114% South Asian · 104/91,086 alleles

Filtering AF 0.0964% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0897%

Overall 0.00818% 132/1,614,082 alleles · rare exomes 126/1,461,876 · genomes 6/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.114%	876
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00186%	53,639
African / African-American	0.00133%	74,930

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.Pro172Leu
Coding: c.515C>T
MANE Select: NM_014489
Type: single nucleotide variant
Location: chr11:3824049 (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.Pro172= Likely benign ★ same residue
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

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-pro172leu (accessed [today's date]).

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