Is APLP1 p.Ala47Glu (c.140C>A) pathogenic?

APLP1 p.Ala47Glu (c.140C>A) is classified Uncertain significance in APLP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0953); Very rare (popmax 0.00803%, afr).

How common is APLP1 p.Ala47Glu (c.140C>A) in the general population?

APLP1 p.Ala47Glu (c.140C>A) is very rare (popmax 0.00803%, afr) (gnomAD).

What do computational predictors say about APLP1 p.Ala47Glu (c.140C>A)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

APLP1 p.Ala47Glu

c.140C>A · VCV4123635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.381	indeterminate
SaProt	LLR -6.96	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 0.61	GERP -1.1, phastCons 0.071
Regional constraint	o/e 1.01	unconstrained · MANE · 3,350 bp · p 0.81 · regional, not allelic
Overall
CADD	21.8	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 0.00803% African / African-American · 5/62,242 alleles

Filtering AF 0.00314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.002%

Overall 0.00039% 5/1,282,514 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: APLP1
Protein: p.Ala47Glu
Coding: c.140C>A
MANE Select: NM_001024807
Type: single nucleotide variant
Location: chr19:35868776 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.36 · 6 PDB

Full APLP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APLP1 p.Ala149Asp Uncertain significance ★ ⚠ same type
APLP1 p.Ala222Pro Uncertain significance ★ ⚠ same type
APLP1 p.Ala263Thr Uncertain significance ★ ⚠ same type
APLP1 p.Ala382Thr Uncertain significance ★ ⚠ same type
APLP1 p.Ala391Val Uncertain significance ★ ⚠ same type
APLP1 p.Ala412Thr Uncertain significance ★ ⚠ same type
APLP1 p.Ala57Val Uncertain significance ★ ⚠ same type
APLP1 p.Arg124Trp 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/aplp1-p-ala47glu (accessed [today's date]).

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