Is APLP2 p.Pro50Ser (c.148C>T) pathogenic?

APLP2 p.Pro50Ser (c.148C>T) is classified Uncertain significance in APLP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.9249); Absent from gnomAD v4.1.

How common is APLP2 p.Pro50Ser (c.148C>T) in the general population?

APLP2 p.Pro50Ser (c.148C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APLP2 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely pathogenic (score 0.9249) — an in-silico prediction, not a clinical call.

APLP2 p.Pro50Ser

c.148C>T · VCV4641670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9249 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9249	likely pathogenic
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -15.30	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 6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 73 kb · p 0.93 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APLP2
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_001142276
Type: single nucleotide variant
Location: chr11:130109471 (GRCh38)
Gene constraint: LOEUF 0.723 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.87 · 3 PDB
Residue 50: the e1 domain; the 'gfld subdomain' region

Full APLP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APLP2 p.Val336Leu Uncertain significance ★★ ⚠ same type
APLP2 c.1837+1543A>G Uncertain significance ★ ⚠ same type
APLP2 c.1837+1550C>T Uncertain significance ★ ⚠ same type
APLP2 c.1837+1564C>A Uncertain significance ★ ⚠ same type
APLP2 c.1837+1564C>T Uncertain significance ★ ⚠ same type
APLP2 c.1837+1567A>G Uncertain significance ★ ⚠ same type
APLP2 c.1837+1571A>G Uncertain significance ★ ⚠ same type
APLP2 p.Ala244Thr Uncertain significance ★ ⚠ 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/aplp2-p-pro50ser (accessed [today's date]).

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