Is ALG6 p.Tyr441= (c.1323T>C) pathogenic?

ALG6 p.Tyr441= (c.1323T>C) is classified Benign/Likely benign in ALG6 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.39%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Tyr441= (c.1323T>C)?

ALG6 p.Tyr441= (c.1323T>C) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Tyr441= (c.1323T>C) in the general population?

ALG6 p.Tyr441= (c.1323T>C) is low-frequency (popmax 1.39%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Tyr441=

c.1323T>C · rs116660078 · VCV95528

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.39%, nfe)

Conditions

ALG6-congenital disorder of glycosylation 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP 0.25, phastCons 0.001
Overall
CADD	4.697	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.39% European (non-Finnish) · 16,135/1,162,368 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.36%

Overall 1.12% 17,769/1,587,532 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.39%	72
Amishnot grpmax-eligible	1.21%	83
Finnishnot grpmax-eligible	0.919%	109
Remaining individualsnot grpmax-eligible	0.898%	111
Admixed American	0.372%	269
African / African-American	0.208%	480
Middle Eastern	0.185%	540
South Asian	0.114%	876
Ashkenazi Jewishnot grpmax-eligible	0.0275%	3,632
East Asian	0.00225%	44,492

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: ALG6
Protein: p.Tyr441=
Coding: c.1323T>C
MANE Select: NM_013339
dbSNP: rs116660078
Type: single nucleotide variant
Location: chr1:63429123 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG6-congenital disorder of glycosylation 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG6-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG6 p.Tyr441Cys Uncertain significance ★ ⚠ same residue
ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+5G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.429+1G>T Likely pathogenic ★★ same condition
ALG6 c.495-2A>G Likely pathogenic ★★ same condition
ALG6 c.495-2A>T Likely pathogenic ★★ 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/alg6-p-tyr441 (accessed [today's date]).

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