Is ALG14 p.Pro65Leu (c.194C>T) pathogenic?

ALG14 p.Pro65Leu (c.194C>T) is classified Pathogenic in ALG14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-03-01). AlphaMissense: likely pathogenic (0.6403); Very rare (popmax 8.48e-05%, nfe); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Pro65Leu (c.194C>T)?

ALG14 p.Pro65Leu (c.194C>T) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Pro65Leu (c.194C>T) in the general population?

ALG14 p.Pro65Leu (c.194C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Congenital myasthenic syndrome inherited?

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

What do computational predictors say about ALG14 p.Pro65Leu (c.194C>T)?

AlphaMissense predicts likely pathogenic (score 0.6403) — an in-silico prediction, not a clinical call.

ALG14 p.Pro65Leu

c.194C>T · rs730882050 · VCV183013

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6403 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.6403	likely pathogenic ✓ concordant with ClinVar
REVEL	0.656	pathogenic-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,734 alleles

Overall 6.84e-05% 1/1,461,456 alleles · very rare

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.Pro65Leu
Coding: c.194C>T
dbSNP: rs730882050
Type: single nucleotide variant
Location: chr1:95064960 (GRCh38)

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)

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-pro65leu (accessed [today's date]).

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