Is ALG1 p.Ala360Val (c.1079C>T) pathogenic?

ALG1 p.Ala360Val (c.1079C>T) is classified Pathogenic/Likely pathogenic in ALG1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-02-19). AlphaMissense: likely pathogenic (0.8058); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Ala360Val (c.1079C>T)?

ALG1 p.Ala360Val (c.1079C>T) is associated with Inborn genetic diseases, ALG1-congenital disorder of glycosylation, congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Ala360Val (c.1079C>T) in the general population?

ALG1 p.Ala360Val (c.1079C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ALG1 p.Ala360Val (c.1079C>T)?

AlphaMissense predicts likely pathogenic (score 0.8058) — an in-silico prediction, not a clinical call.

ALG1 p.Ala360Val

c.1079C>T · rs398124348 · VCV95931

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8058 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8058	likely pathogenic ✓ concordant with ClinVar
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -15.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	24.4	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 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000682% 11/1,611,954 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,314
African / African-American	0.00133%	74,980
South Asian	0.0011%	90,988
European (non-Finnish)	0.000424%	235,968

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.Ala360Val
Coding: c.1079C>T
MANE Select: NM_019109
dbSNP: rs398124348
Type: single nucleotide variant
Location: chr16:5082565 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 360: a UniProt-annotated variant site (in cdg1k; decreased function in protein glycosylation as shown by rescue assays in an alg1-deficient yeast strain)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG1-congenital disorder of glycosylation congenital disorder of glycosylation

Similar variants

ALG1 p.Ala360= Likely benign ★★ 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
ALG1 c.863-2A>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-ala360val (accessed [today's date]).

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