Is ALG14 p.Arg109Gln (c.326G>A) pathogenic?

ALG14 p.Arg109Gln (c.326G>A) is classified Uncertain significance in ALG14 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-22). AlphaMissense: likely pathogenic (0.8284); Ultra-rare (popmax 0.0164%, nfe); Associated with myopathy, epilepsy, and progressive cerebral atrophy.

What condition is associated with ALG14 p.Arg109Gln (c.326G>A)?

ALG14 p.Arg109Gln (c.326G>A) is associated with myopathy, epilepsy, and progressive cerebral atrophy, congenital myasthenic syndrome 15, intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (ClinVar).

How common is ALG14 p.Arg109Gln (c.326G>A) in the general population?

ALG14 p.Arg109Gln (c.326G>A) is ultra-rare (popmax 0.0164%, nfe) (gnomAD).

What do computational predictors say about ALG14 p.Arg109Gln (c.326G>A)?

AlphaMissense predicts likely pathogenic (score 0.8284) — an in-silico prediction, not a clinical call.

ALG14 p.Arg109Gln

c.326G>A · rs199689080 · VCV379351

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8284 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopathy, epilepsy, and progressive cerebral atrophy

Computational evidence

Protein change
AlphaMissense	0.8284	likely pathogenic
REVEL	0.737	pathogenic-leaning
SaProt	LLR -14.66	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% European (non-Finnish) · 193/1,179,994 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.0129% 209/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0164%	6,114
Remaining individualsnot grpmax-eligible	0.0128%	7,813
African / African-American	0.008%	12,505
Admixed American	0.00167%	60,022
South Asian	0.0011%	91,084

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.Arg109Gln
Coding: c.326G>A
MANE Select: NM_144988
dbSNP: rs199689080
Type: single nucleotide variant
Location: chr1:95027223 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.06
Residue 109: a UniProt-annotated variant site (in cms15); a UniProt-annotated variant site (in mepca; uncertain significance; decreased function in dolichol-linked oligosaccharide biosynthetic process)

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 intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Similar variants

ALG14 p.Arg109Trp Uncertain significance ★★ ⚠ same residue
ALG14 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg104Gln 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-arg109gln (accessed [today's date]).

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