Is ALG14 p.Asn144= (c.432C>T) pathogenic?

ALG14 p.Asn144= (c.432C>T) is classified Likely benign in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-20). Ultra-rare (popmax 0.0134%, eas); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Asn144= (c.432C>T)?

ALG14 p.Asn144= (c.432C>T) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Asn144= (c.432C>T) in the general population?

ALG14 p.Asn144= (c.432C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Congenital myasthenic syndrome inherited?

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

ALG14 p.Asn144=

c.432C>T · rs372801574 · VCV1160446

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -4.5
Overall
CADD	2.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,864 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00143% 23/1,613,452 alleles · ultra-rare exomes 21/1,461,248 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,477
African / African-American	0.004%	24,993
Admixed American	0.00167%	59,978
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	90,950
European (non-Finnish)	0.000932%	107,240

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: ALG14
Protein: p.Asn144=
Coding: c.432C>T
MANE Select: NM_144988
dbSNP: rs372801574
Type: single nucleotide variant
Location: chr1:94983295 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 144: a UniProt-annotated variant site (in cms15)

Full ALG14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn82Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu110Lys Uncertain significance ★★ same condition
ALG14 p.Glu179Lys Uncertain significance ★★ ⚠ same condition
ALG14 p.His190Gln Uncertain significance ★★ ⚠ 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/alg14-p-asn144 (accessed [today's date]).

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