Is ALPG p.Tyr412Asp (c.1234T>G) pathogenic?

ALPG p.Tyr412Asp (c.1234T>G) is classified Uncertain significance in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). AlphaMissense: likely pathogenic (0.9289); Very rare (popmax 8.58e-05%, nfe).

How common is ALPG p.Tyr412Asp (c.1234T>G) in the general population?

ALPG p.Tyr412Asp (c.1234T>G) is very rare (popmax 8.58e-05%, nfe) (gnomAD).

What do computational predictors say about ALPG p.Tyr412Asp (c.1234T>G)?

AlphaMissense predicts likely pathogenic (score 0.9289) — an in-silico prediction, not a clinical call.

ALPG p.Tyr412Asp

c.1234T>G · rs1374311427 · VCV3113106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.58e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9289	likely pathogenic · top 8% in ALPG
REVEL	0.681	pathogenic-leaning
SaProt	LLR -13.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.47, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 65 bp · p 0.00059 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.58e-05% European (non-Finnish) · 1/1,165,234 alleles

Overall 0.000687% 1/145,636 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.Tyr412Asp
Coding: c.1234T>G
MANE Select: NM_031313
dbSNP: rs1374311427
Type: single nucleotide variant
Location: chr2:232409382 (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-tyr412asp (accessed [today's date]).

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