Is ALG14 p.Val14Met (c.40G>A) pathogenic?

ALG14 p.Val14Met (c.40G>A) is classified Likely benign in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1269); Rare (popmax 0.284%, afr); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Val14Met (c.40G>A)?

ALG14 p.Val14Met (c.40G>A) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Val14Met (c.40G>A) in the general population?

ALG14 p.Val14Met (c.40G>A) is rare (popmax 0.284%, afr) (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.Val14Met (c.40G>A)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

ALG14 p.Val14Met

c.40G>A · rs11165298 · VCV542125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.284%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -3.1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	17.27	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 0.284% African / African-American · 213/75,052 alleles

Filtering AF 0.252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.24%

Overall 0.0142% 229/1,614,186 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.284%	352
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00999%	10,005

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.Val14Met
Coding: c.40G>A
MANE Select: NM_144988
dbSNP: rs11165298
Type: single nucleotide variant
Location: chr1:95072859 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 14: a UniProt-annotated variant site (in)

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.Val14= Likely benign ★ 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-val14met (accessed [today's date]).

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