Is PGAP1 p.Leu321= (c.963G>A) pathogenic?

PGAP1 p.Leu321= (c.963G>A) is classified Likely benign in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). Very rare (popmax 0.0068%, amr); Associated with Inborn genetic diseases.

What condition is associated with PGAP1 p.Leu321= (c.963G>A)?

PGAP1 p.Leu321= (c.963G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP1 p.Leu321= (c.963G>A) in the general population?

PGAP1 p.Leu321= (c.963G>A) is very rare (popmax 0.0068%, amr) (gnomAD).

PGAP1 p.Leu321=

c.963G>A · VCV3887979

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0068%, amr)

Conditions

Inborn genetic diseases

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 2.1	GERP 0.62, phastCons 1
Overall
CADD	8.306	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0068% Admixed American · 4/58,862 alleles

Filtering AF 0.00321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00289%

Overall 0.00351% 56/1,596,812 alleles · very rare exomes 52/1,444,758 · genomes 4/152,054 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0068%	14,715
European (non-Finnish)	0.00419%	23,849
African / African-American	0.00269%	37,145
Remaining individualsnot grpmax-eligible	0.00162%	61,772

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.Leu321=
Coding: c.963G>A
MANE Select: NM_024989
Type: single nucleotide variant
Location: chr2:196893210 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala714Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala864Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg803His Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg814Cys Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn129Ser Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn363Asp Uncertain significance ★★ ⚠ same condition
PGAP1 p.His261Tyr 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/pgap1-p-leu321 (accessed [today's date]).

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