Is ALG8 p.His93Arg (c.278A>G) pathogenic?

ALG8 p.His93Arg (c.278A>G) is classified Likely benign in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0554); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.His93Arg (c.278A>G)?

ALG8 p.His93Arg (c.278A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ALG8 p.His93Arg (c.278A>G) in the general population?

ALG8 p.His93Arg (c.278A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ALG8 p.His93Arg (c.278A>G)?

AlphaMissense predicts likely benign (score 0.0554) — an in-silico prediction, not a clinical call.

ALG8 p.His93Arg

c.278A>G · VCV4038317

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0554 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0554	likely benign
REVEL	0.258	benign-leaning
SaProt	LLR -5.42	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 -2.6
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	10.48	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

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Overall 6.84e-05% 1/1,461,848 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: ALG8
Protein: p.His93Arg
Coding: c.278A>G
MANE Select: NM_024079
Type: single nucleotide variant
Location: chr11:78124111 (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.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
ALG8 p.Gly130Glu Uncertain significance ★★ ⚠ same condition
ALG8 p.Ile144Phe 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-his93arg (accessed [today's date]).

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