Is ALPG p.Ser301Pro (c.901T>C) pathogenic?

ALPG p.Ser301Pro (c.901T>C) is classified Likely benign in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0474); Very rare (popmax 0.000105%, nfe).

How common is ALPG p.Ser301Pro (c.901T>C) in the general population?

ALPG p.Ser301Pro (c.901T>C) is very rare (popmax 0.000105%, nfe) (gnomAD).

What do computational predictors say about ALPG p.Ser301Pro (c.901T>C)?

AlphaMissense predicts likely benign (score 0.0474) — an in-silico prediction, not a clinical call.

ALPG p.Ser301Pro

c.901T>C · VCV4640086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000105%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0474	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -3.1
Regional constraint	o/e 0.30	constrained · MANE · 275 bp · p 1.7e-07 · regional, not allelic
Overall
CADD	0.003	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 0.000105% European (non-Finnish) · 1/955,892 alleles

Overall 8.1e-05% 1/1,234,648 alleles · very rare

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.Ser301Pro
Coding: c.901T>C
MANE Select: NM_031313
Type: single nucleotide variant
Location: chr2:232408748 (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.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
ALPG p.Ser150= 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-ser301pro (accessed [today's date]).

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