Is ALG14 p.Arg104Ter (c.310C>T) pathogenic?

ALG14 p.Arg104Ter (c.310C>T) is classified Conflicting classifications of pathogenicity in ALG14 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-06-04). Ultra-rare (popmax 0.0114%, nfe); Associated with myopathy, epilepsy, and progressive cerebral atrophy.

How common is ALG14 p.Arg104Ter (c.310C>T) in the general population?

ALG14 p.Arg104Ter (c.310C>T) is ultra-rare (popmax 0.0114%, nfe) (gnomAD).

ALG14 p.Arg104Ter

Q: What condition is associated with ALG14 p.Arg104Ter (c.310C>T)?

ALG14 p.Arg104Ter (c.310C>T) is associated with myopathy, epilepsy, and progressive cerebral atrophy, congenital myasthenic syndrome 15 (ClinVar).

c.310C>T · rs367570129 · VCV183014

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, nfe)

Conditions

myopathy, epilepsy, and progressive cerebral atrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% European (non-Finnish) · 134/1,179,976 alleles

Filtering AF 0.00977% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00912%

Overall 0.00874% 141/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0114%	8,806
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,454
East Asian	0.00223%	44,880
South Asian	0.0022%	45,538

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.Arg104Ter
Coding: c.310C>T
MANE Select: NM_144988
dbSNP: rs367570129
Type: single nucleotide variant
Location: chr1:95027239 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 104: a UniProt-annotated variant site (in cms15)

Full ALG14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myopathy, epilepsy, and progressive cerebral atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 15

Similar variants

ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same residue
ALG14 p.Ala13Ser 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-arg104ter (accessed [today's date]).

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