Is ALG2 p.Asp115Asn (c.343G>A) pathogenic?

ALG2 p.Asp115Asn (c.343G>A) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely pathogenic (0.9666); Very rare (popmax 0.00393%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG2 p.Asp115Asn (c.343G>A)?

ALG2 p.Asp115Asn (c.343G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG2 p.Asp115Asn (c.343G>A) in the general population?

ALG2 p.Asp115Asn (c.343G>A) is very rare (popmax 0.00393%, amr) (gnomAD).

What do computational predictors say about ALG2 p.Asp115Asn (c.343G>A)?

AlphaMissense predicts likely pathogenic (score 0.9666) — an in-silico prediction, not a clinical call.

ALG2 p.Asp115Asn

c.343G>A · rs1322995105 · VCV2241181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00393%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9666	likely pathogenic · top 6% in ALG2
REVEL	0.752	pathogenic-leaning
SaProt	LLR -13.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,957 bp · p 0.038 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00393% Admixed American · 2/50,940 alleles

Filtering AF 0.000651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000244%

Overall 0.000324% 5/1,543,714 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00393%	25,470
European (non-Finnish)	0.000262%	382,080

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: ALG2
Protein: p.Asp115Asn
Coding: c.343G>A
MANE Select: NM_033087
dbSNP: rs1322995105
Type: single nucleotide variant
Location: chr9:99221552 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full ALG2 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

ALG2 p.Ala71Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg393Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Arg7Trp Uncertain significance ★★ ⚠ same condition
ALG2 p.Asp148Gly Uncertain significance ★★ ⚠ same condition
ALG2 p.Cys120Tyr Uncertain significance ★★ ⚠ same condition
ALG2 p.Gln338His Uncertain significance ★★ ⚠ same condition
ALG2 p.Gln406His Uncertain significance ★★ ⚠ same condition
ALG2 p.Glu235Lys 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/alg2-p-asp115asn (accessed [today's date]).

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