Is ALPL p.Arg86Lys (c.257G>A) pathogenic?

ALPL p.Arg86Lys (c.257G>A) is classified Uncertain significance in ALPL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0817); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALPL p.Arg86Lys (c.257G>A)?

ALPL p.Arg86Lys (c.257G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALPL p.Arg86Lys (c.257G>A) in the general population?

ALPL p.Arg86Lys (c.257G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALPL p.Arg86Lys (c.257G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

ALPL p.Arg86Lys

c.257G>A · VCV3533877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.54	GERP -3.5
Regional constraint	o/e 0.83	unconstrained · MANE · 24 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	10.78	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

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: ALPL
Protein: p.Arg86Lys
Coding: c.257G>A
MANE Select: NM_000478
Type: single nucleotide variant
Location: chr1:21561172 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.74 · 5 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALPL p.Arg86= Likely benign ★★ same residue
ALPL p.Gly326Arg Pathogenic/Likely pathogenic ★★ same condition
ALPL p.Gly473Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALPL p.Arg138Trp Uncertain significance ★★ ⚠ same condition
ALPL p.Arg321Gln Uncertain significance ★★ ⚠ same condition
ALPL p.Asn47Lys Uncertain significance ★★ ⚠ same condition
ALPL p.Asp356Glu Uncertain significance ★★ ⚠ same condition
ALPL p.Gly11Asp Uncertain significance ★★ ⚠ same condition

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/alpl-p-arg86lys (accessed [today's date]).

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