Is ALG9 p.Val471Ala (c.1412T>C) pathogenic?

ALG9 p.Val471Ala (c.1412T>C) is classified Uncertain significance in ALG9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-17). AlphaMissense: likely pathogenic (0.6651); Very rare (popmax 0.00133%, afr); Associated with ALG9-related disorder.

What condition is associated with ALG9 p.Val471Ala (c.1412T>C)?

ALG9 p.Val471Ala (c.1412T>C) is associated with ALG9-related disorder (ClinVar).

How common is ALG9 p.Val471Ala (c.1412T>C) in the general population?

ALG9 p.Val471Ala (c.1412T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ALG9 p.Val471Ala (c.1412T>C)?

AlphaMissense predicts likely pathogenic (score 0.6651) — an in-silico prediction, not a clinical call.

ALG9 p.Val471Ala

c.1412T>C · VCV3346849

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG9-related disorder

Computational evidence

Protein change
AlphaMissense	0.6651	likely pathogenic
REVEL	0.377	indeterminate
SaProt	LLR -12.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	23.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V464A vs ClinVar V471A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,070 alleles

Overall 6.2e-05% 1/1,614,124 alleles · very rare exomes 0/1,461,784 · genomes 1/152,340 · joint denominator

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: ALG9
Protein: p.Val471Ala
Coding: c.1412T>C
MANE Select: NM_024740
Type: single nucleotide variant
Location: chr11:111837528 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB

Full ALG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG9-related disorder

Similar variants

ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Ala389Glu Uncertain significance ★ ⚠ same condition
ALG9 p.Arg247Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
ALG9 c.131+6T>A Uncertain significance same condition
ALG9 p.Gly58Arg Uncertain significance ⚠ same condition
ALG9 c.*323A>G Likely benign same condition
ALG9 c.*4C>T Likely benign same condition
ALG9 p.Arg34= Likely benign 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/alg9-p-val471ala (accessed [today's date]).

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