Is ALG1 p.Gln342Pro (c.1025A>C) pathogenic?

ALG1 p.Gln342Pro (c.1025A>C) is classified Pathogenic/Likely pathogenic in ALG1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-29). AlphaMissense: ambiguous (0.4733); Very rare (popmax 0.00512%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Gln342Pro (c.1025A>C)?

ALG1 p.Gln342Pro (c.1025A>C) is associated with Inborn genetic diseases, ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Gln342Pro (c.1025A>C) in the general population?

ALG1 p.Gln342Pro (c.1025A>C) is very rare (popmax 0.00512%, nfe) (gnomAD).

What do computational predictors say about ALG1 p.Gln342Pro (c.1025A>C)?

AlphaMissense predicts ambiguous (score 0.4733) — an in-silico prediction, not a clinical call.

ALG1 p.Gln342Pro

c.1025A>C · rs267606651 · VCV4725

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00512%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4733	ambiguous
REVEL	0.425	indeterminate
SaProt	LLR -11.35	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -1.5, phastCons 0.99
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	19.25	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 0.00512% European (non-Finnish) · 60/1,172,042 alleles

Filtering AF 0.00405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00364%

Overall 0.00426% 61/1,433,072 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00512%	19,534
Remaining individualsnot grpmax-eligible	0.00163%	61,386

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.Gln342Pro
Coding: c.1025A>C
MANE Select: NM_019109
dbSNP: rs267606651
Type: single nucleotide variant
Location: chr16:5081009 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 342: 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

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-gln342pro (accessed [today's date]).

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