Is ALG1 p.His241= (c.723C>T) pathogenic?

ALG1 p.His241= (c.723C>T) is classified Benign in ALG1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele; Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.His241= (c.723C>T)?

ALG1 p.His241= (c.723C>T) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How is ALG1-CDG inherited?

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

ALG1 p.His241=

Q: How common is ALG1 p.His241= (c.723C>T) in the general population?

ALG1 p.His241= (c.723C>T) is common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.723C>T · rs7195893 · VCV198235

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.2%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

ALG1-congenital disorder of glycosylation

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 0.24	GERP -0.2
Overall
CADD	2.445	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.2% Admixed American · 8,492/60,010 alleles

Filtering AF 13.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.8%

Overall 5.72% 91,480/1,599,904 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	14.2%	7
African / African-American	9.57%	10
East Asian	8.57%	12
Amishnot grpmax-eligible	6.48%	15
Middle Eastern	6.44%	16
South Asian	6.43%	16
Ashkenazi Jewishnot grpmax-eligible	6.24%	16
Remaining individualsnot grpmax-eligible	5.63%	18
European (non-Finnish)	4.92%	20
Finnishnot grpmax-eligible	4.59%	22

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: ALG1
Protein: p.His241=
Coding: c.723C>T
MANE Select: NM_019109
dbSNP: rs7195893
Type: single nucleotide variant
Location: chr16:5078000 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.630-2A>G Likely pathogenic ★★ same condition
ALG1 c.863-2A>G Likely pathogenic ★★ same condition
ALG1 c.961+1G>A 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/alg1-p-his241 (accessed [today's date]).

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