Is ALG14 p.Leu37= (c.111C>T) pathogenic?

ALG14 p.Leu37= (c.111C>T) is classified Likely benign in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-23). Very rare (popmax 0.00167%, amr); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Leu37= (c.111C>T)?

ALG14 p.Leu37= (c.111C>T) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Leu37= (c.111C>T) in the general population?

ALG14 p.Leu37= (c.111C>T) is very rare (popmax 0.00167%, amr) (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.Leu37=

c.111C>T · rs1035901315 · VCV1139102

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 4.7	GERP 2.1, phastCons 1
Overall
CADD	14.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,014 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,888 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,014
European (non-Finnish)	0.000339%	295,009

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.Leu37=
Coding: c.111C>T
MANE Select: NM_144988
dbSNP: rs1035901315
Type: single nucleotide variant
Location: chr1:95072788 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06

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.Leu37Phe 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-leu37 (accessed [today's date]).

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