Is ALG9 p.Arg517Trp (c.1549C>T) pathogenic?

ALG9 p.Arg517Trp (c.1549C>T) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1566); Very rare (popmax 0.00445%, eas); Associated with Inborn genetic diseases.

What condition is associated with ALG9 p.Arg517Trp (c.1549C>T)?

ALG9 p.Arg517Trp (c.1549C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ALG9 p.Arg517Trp (c.1549C>T) in the general population?

ALG9 p.Arg517Trp (c.1549C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about ALG9 p.Arg517Trp (c.1549C>T)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

ALG9 p.Arg517Trp

c.1549C>T · rs1040960434 · VCV2333068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	24.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R510W vs ClinVar R517W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,894 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00308% 45/1,461,730 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,447
European (non-Finnish)	0.00356%	28,094
Remaining individualsnot grpmax-eligible	0.0016%	62,464

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.Arg517Trp
Coding: c.1549C>T
MANE Select: NM_024740
dbSNP: rs1040960434
Type: single nucleotide variant
Location: chr11:111836218 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG9 p.Arg517Gln Uncertain significance ★★ ⚠ same residue
ALG9 p.Arg517Leu Benign ⚠ same residue
ALG9 p.Arg607Gln Uncertain significance ★★ ⚠ same condition
ALG9 p.Gln526Glu Uncertain significance ★★ ⚠ same condition
ALG9 p.Ile130Val Uncertain significance ★★ ⚠ same condition
ALG9 p.Ser17Thr Uncertain significance ★★ ⚠ same condition
ALG9 p.Ala421Pro Uncertain significance ★ ⚠ same condition
ALG9 p.Arg42Trp 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/alg9-p-arg517trp (accessed [today's date]).

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