Is ALG1 p.Val144Met (c.430G>A) pathogenic?

ALG1 p.Val144Met (c.430G>A) is classified Uncertain significance in ALG1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-18). AlphaMissense: likely benign (0.2132); Ultra-rare (popmax 0.012%, afr); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Val144Met (c.430G>A)?

ALG1 p.Val144Met (c.430G>A) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Val144Met (c.430G>A) in the general population?

ALG1 p.Val144Met (c.430G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is ALG1-CDG inherited?

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

What do computational predictors say about ALG1 p.Val144Met (c.430G>A)?

AlphaMissense predicts likely benign (score 0.2132) — an in-silico prediction, not a clinical call.

ALG1 p.Val144Met

c.430G>A · rs770392954 · VCV1511378

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2132	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -8.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.6, phastCons 0.81
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	25.4	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 0.012% African / African-American · 9/74,866 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00254% 41/1,613,956 alleles · ultra-rare exomes 39/1,461,894 · genomes 2/152,062 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Remaining individualsnot grpmax-eligible	0.0096%	10,414
South Asian	0.0022%	45,543
European (non-Finnish)	0.00203%	49,168

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.Val144Met
Coding: c.430G>A
MANE Select: NM_019109
dbSNP: rs770392954
Type: single nucleotide variant
Location: chr16:5075427 (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-val144met (accessed [today's date]).

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