Is ALPG p.Arg498Pro (c.1493G>C) pathogenic?

ALPG p.Arg498Pro (c.1493G>C) is classified Benign in ALPG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0566); Common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ALPG p.Arg498Pro (c.1493G>C)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

ALPG p.Arg498Pro

Q: How common is ALPG p.Arg498Pro (c.1493G>C) in the general population?

ALPG p.Arg498Pro (c.1493G>C) is common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1493G>C · rs61730278 · VCV770699

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -3.74	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 -0.32	GERP -2.4
Regional constraint	o/e 0.83	unconstrained · MANE · 465 bp · p 0.026 · regional, not allelic
Overall
CADD	4.126	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 12.1% East Asian · 5,302/43,820 alleles

Filtering AF 11.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.7%

Overall 6.59% 103,136/1,565,572 alleles · common exomes 90,693/1,413,480 · genomes 12,443/152,092 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	12.1%	8
Ashkenazi Jewishnot grpmax-eligible	9.54%	10
African / African-American	9.03%	11
Middle Eastern	8.19%	12
Remaining individualsnot grpmax-eligible	7.34%	14
Finnishnot grpmax-eligible	6.36%	16
European (non-Finnish)	6.25%	16
South Asian	6.08%	16
Amishnot grpmax-eligible	5.92%	17
Admixed American	4.68%	21

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.Arg498Pro
Coding: c.1493G>C
MANE Select: NM_031313
dbSNP: rs61730278
Type: single nucleotide variant
Location: chr2:232409766 (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.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
ALPG p.Ser150= Benign ★★ same type
ALPG p.Tyr95Phe 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-arg498pro (accessed [today's date]).

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