Is ALG6 p.His344= (c.1032T>C) pathogenic?

ALG6 p.His344= (c.1032T>C) is classified Likely benign in ALG6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0373%, afr); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.His344= (c.1032T>C)?

ALG6 p.His344= (c.1032T>C) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.His344= (c.1032T>C) in the general population?

ALG6 p.His344= (c.1032T>C) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.His344=

c.1032T>C · rs146265933 · VCV990163

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

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	<0.2	all four deltas below 0.2 · T>G here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.1	GERP -0.8, phastCons 0.84
Overall
CADD	6.977	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/74,982 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0018% 29/1,609,568 alleles · ultra-rare exomes 14/1,457,294 · genomes 15/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,678
Admixed American	0.00167%	59,856

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.His344=
Coding: c.1032T>C
MANE Select: NM_013339
dbSNP: rs146265933
Type: single nucleotide variant
Location: chr1:63419414 (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.His344Arg Uncertain significance ★ ⚠ same residue
ALG6 p.His344fs Pathogenic ★ 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

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-his344 (accessed [today's date]).

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