Is ALPG p.Pro509Ser (c.1525C>T) pathogenic?

ALPG p.Pro509Ser (c.1525C>T) is classified Uncertain significance in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: likely benign (0.0691); Very rare (popmax 0.00687%, amr).

How common is ALPG p.Pro509Ser (c.1525C>T) in the general population?

ALPG p.Pro509Ser (c.1525C>T) is very rare (popmax 0.00687%, amr) (gnomAD).

What do computational predictors say about ALPG p.Pro509Ser (c.1525C>T)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

ALPG p.Pro509Ser

c.1525C>T · rs781457495 · VCV3113141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -7.30	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 -20	GERP -2.4
Regional constraint	o/e 0.83	unconstrained · MANE · 465 bp · p 0.026 · regional, not allelic
Overall
CADD	0.902	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 0.00687% Admixed American · 4/58,252 alleles

Filtering AF 0.0023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000626% 10/1,597,722 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00687%	14,563
European (non-Finnish)	0.000511%	195,575

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.Pro509Ser
Coding: c.1525C>T
MANE Select: NM_031313
dbSNP: rs781457495
Type: single nucleotide variant
Location: chr2:232409798 (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.Pro509Ala 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-pro509ser (accessed [today's date]).

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