Is ALG9 p.Tyr87His (c.259T>C) pathogenic?

ALG9 p.Tyr87His (c.259T>C) is classified Likely benign in ALG9 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely pathogenic (0.9842); Absent from gnomAD v4.1; Associated with ALG9-related disorder.

What condition is associated with ALG9 p.Tyr87His (c.259T>C)?

ALG9 p.Tyr87His (c.259T>C) is associated with ALG9-related disorder (ClinVar).

How common is ALG9 p.Tyr87His (c.259T>C) in the general population?

ALG9 p.Tyr87His (c.259T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALG9 p.Tyr87His (c.259T>C)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

ALG9 p.Tyr87His

c.259T>C · rs1472089174 · VCV3029585

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG9-related disorder

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic · top 8% in ALG9
REVEL	0.558	indeterminate
SaProt	LLR -14.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.019 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG9
Protein: p.Tyr87His
Coding: c.259T>C
MANE Select: NM_024740
dbSNP: rs1472089174
Type: single nucleotide variant
Location: chr11:111870243 (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.Tyr87= Likely benign ★ same residue
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 p.Val471Ala Uncertain significance ⚠ same condition
ALG9 c.*323A>G 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-tyr87his (accessed [today's date]).

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