Is ALG14 p.Ser38Ile (c.113G>T) pathogenic?

ALG14 p.Ser38Ile (c.113G>T) is classified Conflicting classifications of pathogenicity in ALG14 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-01). AlphaMissense: ambiguous (0.4396); Rare (popmax 0.393%, nfe); Associated with congenital myasthenic syndrome 15.

What condition is associated with ALG14 p.Ser38Ile (c.113G>T)?

ALG14 p.Ser38Ile (c.113G>T) is associated with congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Ser38Ile (c.113G>T) in the general population?

ALG14 p.Ser38Ile (c.113G>T) is rare (popmax 0.393%, 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.Ser38Ile (c.113G>T)?

AlphaMissense predicts ambiguous (score 0.4396) — an in-silico prediction, not a clinical call.

ALG14 p.Ser38Ile

c.113G>T · rs139521179 · VCV287329

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

ambiguous

0.4396 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.393%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

congenital myasthenic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.4396	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -9.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -1.7, phastCons 0.94
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	22.8	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 0.393% European (non-Finnish) · 4,639/1,180,030 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.307% 4,961/1,614,186 alleles · rare exomes 4,621/1,461,878 · genomes 340/152,308 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.393%	254
Remaining individualsnot grpmax-eligible	0.261%	383
Admixed American	0.142%	706
Middle Eastern	0.066%	1,516
African / African-American	0.0586%	1,706
Finnishnot grpmax-eligible	0.0359%	2,784
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0022%	45,542

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.Ser38Ile
Coding: c.113G>T
MANE Select: NM_144988
dbSNP: rs139521179
Type: single nucleotide variant
Location: chr1:95072786 (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.Ser38Asn 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-ser38ile (accessed [today's date]).

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