Is ALG11 p.Arg15Thr (c.44G>C) pathogenic?

ALG11 p.Arg15Thr (c.44G>C) is classified Uncertain significance in ALG11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-10-12). AlphaMissense: likely benign (0.1806); Ultra-rare (popmax 0.0111%, nfe); Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with ALG11 p.Arg15Thr (c.44G>C)?

ALG11 p.Arg15Thr (c.44G>C) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is ALG11 p.Arg15Thr (c.44G>C) in the general population?

ALG11 p.Arg15Thr (c.44G>C) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

How is ALG11-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ALG11 p.Arg15Thr (c.44G>C)?

AlphaMissense predicts likely benign (score 0.1806) — an in-silico prediction, not a clinical call.

ALG11 p.Arg15Thr

c.44G>C · rs139798579 · VCV312409

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1806	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.52	donor loss · deltas
Pangolin	Δ0.60	loss · gain 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.068 · regional, not allelic
Overall
CADD	32.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% European (non-Finnish) · 131/1,180,046 alleles

Filtering AF 0.00952% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00896%

Overall 0.00843% 136/1,614,058 alleles · ultra-rare exomes 130/1,461,810 · genomes 6/152,248 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0111%	9,008
Finnishnot grpmax-eligible	0.00625%	16,011
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: ALG11
Protein: p.Arg15Thr
Coding: c.44G>C
MANE Select: NM_001004127
dbSNP: rs139798579
Type: single nucleotide variant
Location: chr13:52012462 (GRCh38)
Gene constraint: LOEUF 0.908 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.40

Full ALG11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG11-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG11-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG11 c.45-2A>T Likely pathogenic ★★ same condition
ALG11 p.Arg468Cys Likely pathogenic ★★ ⚠ same condition
ALG11 p.Arg468His Likely pathogenic ★★ same condition
ALG11 p.Met1Val Likely pathogenic ★★ same condition
ALG11 c.*540T>A Uncertain significance ★★ ⚠ same condition
ALG11 p.Arg136Cys Uncertain significance ★★ same condition
ALG11 p.Arg346His Uncertain significance ★★ ⚠ same condition
ALG11 p.Asn257Ser 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/alg11-p-arg15thr (accessed [today's date]).

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