Is PGAP3 p.Ser111= (c.333G>A) pathogenic?

PGAP3 p.Ser111= (c.333G>A) is classified Benign/Likely benign in PGAP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-13). Ultra-rare (popmax 0.0132%, sas).

How common is PGAP3 p.Ser111= (c.333G>A) in the general population?

PGAP3 p.Ser111= (c.333G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

PGAP3 p.Ser111=

c.333G>A · rs143327410 · VCV1701320

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.43	GERP -4.4, phastCons 0.001
Overall
CADD	8.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,012 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00855% 138/1,613,594 alleles · ultra-rare exomes 125/1,461,322 · genomes 13/152,272 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.233%	429
Remaining individualsnot grpmax-eligible	0.0304%	3,286
South Asiangrpmax	0.0132%	7,584
European (non-Finnish)	0.00314%	31,887
East Asian	0.00223%	44,854

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PGAP3
Protein: p.Ser111=
Coding: c.333G>A
MANE Select: NM_033419
dbSNP: rs143327410
Type: single nucleotide variant
Location: chr17:39684696 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.17

Full PGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAP3 p.Ser111Leu Uncertain significance ★ ⚠ same residue
PGAP3 c.558-10G>A Pathogenic/Likely pathogenic ★★ same type
PGAP3 c.694+1G>A Pathogenic ★★ same type
PGAP3 p.Asp305Gly Pathogenic/Likely pathogenic ★★ same type
PGAP3 p.Gln89Ter Pathogenic ★★ same type
PGAP3 p.Glu37Ter Pathogenic ★★ same type
PGAP3 p.His284Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
PGAP3 p.His284Tyr Pathogenic/Likely pathogenic ★★ 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/pgap3-p-ser111 (accessed [today's date]).

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