Is ALG14 p.Gly57= (c.171G>A) pathogenic?

ALG14 p.Gly57= (c.171G>A) is classified Benign in ALG14 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). Low-frequency (popmax 1.79%, eas); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Gly57= (c.171G>A)?

ALG14 p.Gly57= (c.171G>A) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Gly57= (c.171G>A) in the general population?

ALG14 p.Gly57= (c.171G>A) is low-frequency (popmax 1.79%, 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.Gly57=

c.171G>A · rs141065009 · VCV475362

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.032	GERP -1.5, phastCons 0.32
Overall
CADD	7.592	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.79% East Asian · 804/44,852 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.65%

Overall 0.0545% 879/1,613,446 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.79%	56
Remaining individualsnot grpmax-eligible	0.0688%	1,453
South Asian	0.022%	4,550
Middle Eastern	0.0165%	6,062
African / African-American	0.008%	12,497
Admixed American	0.00167%	59,982
European (non-Finnish)	0.000339%	294,910

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.Gly57=
Coding: c.171G>A
MANE Select: NM_144988
dbSNP: rs141065009
Type: single nucleotide variant
Location: chr1:95064983 (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.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-gly57 (accessed [today's date]).

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