Is PGAP3 p.His91Arg (c.272A>G) pathogenic?

PGAP3 p.His91Arg (c.272A>G) is classified Uncertain significance in PGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-24). AlphaMissense: ambiguous (0.4075); Ultra-rare (popmax 0.035%, amr).

How common is PGAP3 p.His91Arg (c.272A>G) in the general population?

PGAP3 p.His91Arg (c.272A>G) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about PGAP3 p.His91Arg (c.272A>G)?

AlphaMissense predicts ambiguous (score 0.4075) — an in-silico prediction, not a clinical call.

PGAP3 p.His91Arg

c.272A>G · rs527343773 · VCV2187815

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4075	ambiguous
REVEL	0.886	moderately pathogenic-leaning
SaProt	LLR -10.18	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 15 kb · p 0.63 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/59,984 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00279% 45/1,612,892 alleles · ultra-rare exomes 39/1,460,596 · genomes 6/152,296 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,856
European (non-Finnish)	0.00195%	51,268
African / African-American	0.00133%	74,990

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.His91Arg
Coding: c.272A>G
MANE Select: NM_033419
dbSNP: rs527343773
Type: single nucleotide variant
Location: chr17:39685929 (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 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
PGAP3 p.Pro105Gln 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-his91arg (accessed [today's date]).

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