Is ALG8 p.Asn12Ser (c.35A>G) pathogenic?

ALG8 p.Asn12Ser (c.35A>G) is classified Uncertain significance in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.0624); No allele count reported in gnomAD v4.1 (AN 1,561,844); Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.Asn12Ser (c.35A>G)?

ALG8 p.Asn12Ser (c.35A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG8 p.Asn12Ser (c.35A>G) in the general population?

ALG8 p.Asn12Ser (c.35A>G) is no allele count reported in gnomAD v4.1 (AN 1,561,844) (gnomAD).

What do computational predictors say about ALG8 p.Asn12Ser (c.35A>G)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

ALG8 p.Asn12Ser

c.35A>G · VCV4038388

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,561,844)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -1.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -1.8	GERP -2.2
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	6.759	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

No allele count reported in gnomAD v4.1 (AN 1,561,844). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALG8
Protein: p.Asn12Ser
Coding: c.35A>G
MANE Select: NM_024079
Type: single nucleotide variant
Location: chr11:78139554 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07

Full ALG8 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

ALG8 p.Asn12Tyr Uncertain significance ★ ⚠ same residue
ALG8 p.Asn12= Conflicting classifications of pathogenicity ★ same residue
ALG8 p.Ala250Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala388Pro Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala424Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Ala72Val Uncertain significance ★★ ⚠ same condition
ALG8 p.Arg215Gln 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/alg8-p-asn12ser (accessed [today's date]).

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