Is ALG9 p.Glu44Asp (c.132G>T) pathogenic?

ALG9 p.Glu44Asp (c.132G>T) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). AlphaMissense: likely benign (0.1112); Very rare (popmax 0.00158%, afr).

How common is ALG9 p.Glu44Asp (c.132G>T) in the general population?

ALG9 p.Glu44Asp (c.132G>T) is very rare (popmax 0.00158%, afr) (gnomAD).

What do computational predictors say about ALG9 p.Glu44Asp (c.132G>T)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

ALG9 p.Glu44Asp

c.132G>T · rs782467173 · VCV2429663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00158%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.73	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 0.38	GERP -0.27, phastCons 0.032
Regional constraint	o/e 0.88	unconstrained · MANE · 27 kb · p 0.019 · regional, not allelic
Overall
CADD	20.9	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 0.00158% African / African-American · 1/63,326 alleles

Overall 0.000733% 1/136,350 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: ALG9
Protein: p.Glu44Asp
Coding: c.132G>T
MANE Select: NM_024740
dbSNP: rs782467173
Type: single nucleotide variant
Location: chr11:111870370 (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

Similar variants

ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same type
ALG9 c.896-2A>G Likely pathogenic ★★ same type
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same type
ALG9 p.Trp248Ter Pathogenic/Likely pathogenic ★★ same type
ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same type
ALG9 c.*1607C>T Uncertain significance ★★ same type
ALG9 c.*1624A>C Uncertain significance ★★ same type
ALG9 c.*1722C>T Uncertain significance ★★ same type

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-glu44asp (accessed [today's date]).

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