Is ALG1 p.Ser267Asn (c.800G>A) pathogenic?

ALG1 p.Ser267Asn (c.800G>A) is classified Benign/Likely benign in ALG1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0864); Common (popmax 21%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Kabuki syndrome 1.

What condition is associated with ALG1 p.Ser267Asn (c.800G>A)?

ALG1 p.Ser267Asn (c.800G>A) is associated with Kabuki syndrome 1, ALG1-congenital disorder of glycosylation (ClinVar).

What do computational predictors say about ALG1 p.Ser267Asn (c.800G>A)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

ALG1 p.Ser267Asn

Q: How common is ALG1 p.Ser267Asn (c.800G>A) in the general population?

ALG1 p.Ser267Asn (c.800G>A) is common (popmax 21%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.800G>A · rs17849848 · VCV166669

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kabuki syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.76, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21% Admixed American · 12,615/59,996 alleles

Filtering AF 20.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.6%

Overall 8.07% 130,115/1,612,546 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	21%	5
East Asian	14.8%	7
Finnishnot grpmax-eligible	8.64%	12
Ashkenazi Jewishnot grpmax-eligible	8.18%	12
European (non-Finnish)	7.96%	13
Remaining individualsnot grpmax-eligible	7.64%	13
Amishnot grpmax-eligible	5.48%	18
Middle Eastern	4.12%	24
South Asian	3.16%	32
African / African-American	1.44%	69

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.Ser267Asn
Coding: c.800G>A
MANE Select: NM_019109
dbSNP: rs17849848
Type: single nucleotide variant
Location: chr16:5078816 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 267: a UniProt-annotated variant site (no effect on function in protein glycosylation)

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

Disease context

Kabuki syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG1-congenital disorder of glycosylation

Similar variants

ALG1 p.Ser267= Likely benign ★★ same residue
ALG1 p.Ser267Arg Uncertain significance ★ ⚠ same residue
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

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-ser267asn (accessed [today's date]).

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