Is ALG3 p.Lys7Asn (c.21A>C) pathogenic?

ALG3 p.Lys7Asn (c.21A>C) is classified Uncertain significance in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.4954); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ALG3 p.Lys7Asn (c.21A>C)?

ALG3 p.Lys7Asn (c.21A>C) is associated with Inborn genetic diseases (ClinVar).

How common is ALG3 p.Lys7Asn (c.21A>C) in the general population?

ALG3 p.Lys7Asn (c.21A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG3 p.Lys7Asn (c.21A>C)?

AlphaMissense predicts ambiguous (score 0.4954) — an in-silico prediction, not a clinical call.

ALG3 p.Lys7Asn

c.21A>C · rs992372429 · VCV2229899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4954 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4954	ambiguous
REVEL	0.311	indeterminate
SaProt	LLR -6.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -0.55
Regional constraint	o/e 1.09	unconstrained · MANE · 3,742 bp · p 0.14 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

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: ALG3
Protein: p.Lys7Asn
Coding: c.21A>C
MANE Select: NM_005787
dbSNP: rs992372429
Type: single nucleotide variant
Location: chr3:184248920 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 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

ALG3 p.Lys7Gln Uncertain significance ★★ ⚠ same residue
ALG3 p.Ala102Ser Uncertain significance ★★ ⚠ same condition
ALG3 p.Arg229Cys Uncertain significance ★★ ⚠ same condition
ALG3 p.Arg27Gly Uncertain significance ★★ ⚠ same condition
ALG3 p.Arg378Cys Uncertain significance ★★ ⚠ same condition
ALG3 p.Asn83Ser Uncertain significance ★★ ⚠ same condition
ALG3 p.Cys21Gly Uncertain significance ★★ ⚠ same condition
ALG3 p.Cys21Phe 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/alg3-p-lys7asn (accessed [today's date]).

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