Is ALG6 p.Phe327= (c.981T>C) pathogenic?

ALG6 p.Phe327= (c.981T>C) is classified Benign in ALG6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Phe327= (c.981T>C)?

ALG6 p.Phe327= (c.981T>C) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How is ALG6-CDG inherited?

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

ALG6 p.Phe327=

Q: How common is ALG6 p.Phe327= (c.981T>C) in the general population?

ALG6 p.Phe327= (c.981T>C) is common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.981T>C · rs75451833 · VCV128355

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 13.1%, afr) — too common for a highly-penetrant pathogenic allele

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 0.093	GERP -2.1, phastCons 0.97
Overall
CADD	5.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.1% African / African-American · 9,813/74,672 alleles

Filtering AF 12.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.8%

Overall 0.715% 11,469/1,604,276 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.1%	8
Remaining individualsnot grpmax-eligible	0.922%	108
Admixed American	0.88%	114
Middle Eastern	0.763%	131
European (non-Finnish)	0.041%	2,441
South Asian	0.0308%	3,245
Finnishnot grpmax-eligible	0.00156%	64,000

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.Phe327=
Coding: c.981T>C
MANE Select: NM_013339
dbSNP: rs75451833
Type: single nucleotide variant
Location: chr1:63415951 (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 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
ALG6 c.680+1G>A Pathogenic/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-phe327 (accessed [today's date]).

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