Is ALG9 p.Ser17Thr (c.50G>C) pathogenic?

ALG9 p.Ser17Thr (c.50G>C) is classified Uncertain significance in ALG9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-04). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.0027%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG9 p.Ser17Thr (c.50G>C)?

ALG9 p.Ser17Thr (c.50G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ALG9 p.Ser17Thr (c.50G>C) in the general population?

ALG9 p.Ser17Thr (c.50G>C) is very rare (popmax 0.0027%, nfe) (gnomAD).

What do computational predictors say about ALG9 p.Ser17Thr (c.50G>C)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

ALG9 p.Ser17Thr

c.50G>C · rs878853116 · VCV235812

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.60	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 2.2	GERP -0.92, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.019 · regional, not allelic
Overall
CADD	20.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0027% European (non-Finnish) · 31/1,146,710 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00208% 32/1,536,450 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0027%	36,991
Remaining individualsnot grpmax-eligible	0.00167%	59,962

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.Ser17Thr
Coding: c.50G>C
MANE Select: NM_024740
dbSNP: rs878853116
Type: single nucleotide variant
Location: chr11:111871433 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB
Residue 17: the 'disordered' region

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.Arg607Gln Uncertain significance ★★ ⚠ same condition
ALG9 p.Gln526Glu Uncertain significance ★★ ⚠ same condition
ALG9 p.Ile130Val Uncertain significance ★★ ⚠ same condition
ALG9 p.Ala421Pro Uncertain significance ★ ⚠ same condition
ALG9 p.Arg42Trp Uncertain significance ★ ⚠ same condition
ALG9 p.Arg517Trp Uncertain significance ★ ⚠ same condition
ALG9 p.Arg584Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
ALG9 p.Gly37Asp 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-ser17thr (accessed [today's date]).

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