Is ALPG p.Arg33His (c.98G>A) pathogenic?

ALPG p.Arg33His (c.98G>A) is classified Uncertain significance in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.025%, amr).

How common is ALPG p.Arg33His (c.98G>A) in the general population?

ALPG p.Arg33His (c.98G>A) is ultra-rare (popmax 0.025%, amr) (gnomAD).

What do computational predictors say about ALPG p.Arg33His (c.98G>A)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

ALPG p.Arg33His

c.98G>A · rs776010626 · VCV3113209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -3.7
Regional constraint	o/e 1.03	unconstrained · MANE · 1,395 bp · p 0.6 · regional, not allelic
Overall
CADD	0.149	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/59,980 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00155% 25/1,613,636 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
East Asian	0.00669%	14,956
African / African-American	0.00401%	24,947
South Asian	0.0033%	30,323
European (non-Finnish)	8.47e-05%	1,179,966

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: ALPG
Protein: p.Arg33His
Coding: c.98G>A
MANE Select: NM_031313
dbSNP: rs776010626
Type: single nucleotide variant
Location: chr2:232407087 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.31

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

Similar variants

ALPG p.Arg33Cys Uncertain significance ★ ⚠ same residue
ALPG p.Arg498Pro Benign ★★ same type
ALPG p.Gly230= Benign ★★ same type
ALPG p.Gly500Asp Likely benign ★★ same type
ALPG p.His172= Benign/Likely benign ★★ same type
ALPG p.Leu8= Benign ★★ same type
ALPG p.Pro228Arg Benign ★★ ⚠ same type
ALPG p.Pro94Ser Benign ★★ ⚠ 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/alpg-p-arg33his (accessed [today's date]).

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