Is ALG1 p.Lys439Arg (c.1316A>G) pathogenic?

ALG1 p.Lys439Arg (c.1316A>G) is classified Uncertain significance in ALG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0666); Very rare (popmax 0.000848%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Lys439Arg (c.1316A>G)?

ALG1 p.Lys439Arg (c.1316A>G) is associated with Inborn genetic diseases, ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Lys439Arg (c.1316A>G) in the general population?

ALG1 p.Lys439Arg (c.1316A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about ALG1 p.Lys439Arg (c.1316A>G)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

ALG1 p.Lys439Arg

c.1316A>G · rs1281758881 · VCV1425428

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.88	GERP 0.77, phastCons 0.035
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	10.44	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 0.000848% European (non-Finnish) · 10/1,179,782 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000692% 10/1,444,132 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: ALG1
Protein: p.Lys439Arg
Coding: c.1316A>G
MANE Select: NM_201400 · reported on NM_019109
dbSNP: rs1281758881
Type: single nucleotide variant
Location: chr16:5084802 (GRCh38)

Full ALG1 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

Also linked: ALG1-congenital disorder of glycosylation

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/alg1-p-lys439arg (accessed [today's date]).

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