Is ALG1 p.Pro430Thr (c.1288C>A) pathogenic?

ALG1 p.Pro430Thr (c.1288C>A) is classified Uncertain significance in ALG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-24). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.0334%, afr); Associated with Inborn genetic diseases.

What condition is associated with ALG1 p.Pro430Thr (c.1288C>A)?

ALG1 p.Pro430Thr (c.1288C>A) is associated with Inborn genetic diseases, ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Pro430Thr (c.1288C>A) in the general population?

ALG1 p.Pro430Thr (c.1288C>A) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

What do computational predictors say about ALG1 p.Pro430Thr (c.1288C>A)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

ALG1 p.Pro430Thr

c.1288C>A · rs376032057 · VCV3110420

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	14.77	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 25/74,846 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00445% 71/1,596,330 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0334%	2,994
Remaining individualsnot grpmax-eligible	0.00804%	12,440
Admixed American	0.00333%	29,998
European (non-Finnish)	0.00322%	31,047
East Asian	0.00223%	44,886

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.Pro430Thr
Coding: c.1288C>A
MANE Select: NM_201400 · reported on NM_019109
dbSNP: rs376032057
Type: single nucleotide variant
Location: chr16:5084774 (GRCh38)

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

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-pro430thr (accessed [today's date]).

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