Is ALG14 p.Ser184= (c.552C>T) pathogenic?

ALG14 p.Ser184= (c.552C>T) is classified Likely benign in ALG14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-01). Rare (popmax 0.223%, afr); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Ser184= (c.552C>T)?

ALG14 p.Ser184= (c.552C>T) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Ser184= (c.552C>T) in the general population?

ALG14 p.Ser184= (c.552C>T) is rare (popmax 0.223%, afr) (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.Ser184=

c.552C>T · rs148202016 · VCV475366

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.223%, afr)

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.096	GERP -4.5, phastCons 0.086
Overall
CADD	11.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.223% African / African-American · 167/75,014 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0135% 218/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.223%	449
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.00667%	15,003
European (non-Finnish)	0.00246%	40,690
East Asian	0.00223%	44,872
South Asian	0.0022%	45,540
Finnishnot grpmax-eligible	0.00156%	64,002

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.Ser184=
Coding: c.552C>T
MANE Select: NM_144988
dbSNP: rs148202016
Type: single nucleotide variant
Location: chr1:94983175 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 184: 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.Ser184Cys Uncertain significance ★ ⚠ same residue
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

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-ser184 (accessed [today's date]).

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