Is ALG8 p.Val321Ile (c.961G>A) pathogenic?

ALG8 p.Val321Ile (c.961G>A) is classified Uncertain significance in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-16). AlphaMissense: likely benign (0.1319); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG8 p.Val321Ile (c.961G>A)?

ALG8 p.Val321Ile (c.961G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ALG8 p.Val321Ile (c.961G>A) in the general population?

ALG8 p.Val321Ile (c.961G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ALG8 p.Val321Ile (c.961G>A)?

AlphaMissense predicts likely benign (score 0.1319) — an in-silico prediction, not a clinical call.

ALG8 p.Val321Ile

c.961G>A · rs767311729 · VCV2289821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1319 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1319	likely benign
REVEL	0.486	indeterminate
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	24.4	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 0.00133% African / African-American · 1/75,024 alleles

Overall 6.84e-05% 1/1,461,852 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.Val321Ile
Coding: c.961G>A
MANE Select: NM_024079
dbSNP: rs767311729
Type: single nucleotide variant
Location: chr11:78109519 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 321: a UniProt-annotated variant site (in pcld3)

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-val321ile (accessed [today's date]).

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