Is APLP1 p.Asp506Val (c.1517A>T) pathogenic?

APLP1 p.Asp506Val (c.1517A>T) is classified Uncertain significance in APLP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0272%, amr).

How common is APLP1 p.Asp506Val (c.1517A>T) in the general population?

APLP1 p.Asp506Val (c.1517A>T) is ultra-rare (popmax 0.0272%, amr) (gnomAD).

What do computational predictors say about APLP1 p.Asp506Val (c.1517A>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

APLP1 p.Asp506Val

c.1517A>T · VCV3931285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0272%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.2	GERP 0.73, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 7,407 bp · p 0.0044 · regional, not allelic
Overall
CADD	22.0	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 0.0272% Admixed American · 16/58,772 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.00106% 17/1,610,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0272%	3,673
Remaining individualsnot grpmax-eligible	0.0016%	62,354

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.Asp506Val
Coding: c.1517A>T
MANE Select: NM_001024807
Type: single nucleotide variant
Location: chr19:35877790 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.36 · 6 PDB
Residue 506: the 'disordered' region

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.Ala47Glu Uncertain significance ★ ⚠ same type
APLP1 p.Ala57Val 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-asp506val (accessed [today's date]).

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