Is ALG14 p.Ala13Ser (c.37G>T) pathogenic?

ALG14 p.Ala13Ser (c.37G>T) is classified Uncertain significance in ALG14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1229); Very rare (popmax 0.00659%, sas); Associated with myopathy, epilepsy, and progressive cerebral atrophy.

What condition is associated with ALG14 p.Ala13Ser (c.37G>T)?

ALG14 p.Ala13Ser (c.37G>T) is associated with myopathy, epilepsy, and progressive cerebral atrophy (ClinVar).

How common is ALG14 p.Ala13Ser (c.37G>T) in the general population?

ALG14 p.Ala13Ser (c.37G>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ALG14 p.Ala13Ser (c.37G>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

ALG14 p.Ala13Ser

c.37G>T · rs760001852 · VCV3234955

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopathy, epilepsy, and progressive cerebral atrophy

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -7.40	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 0.25	GERP -1.7
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	11.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00659% South Asian · 6/91,082 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00226% 33/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,180
European (non-Finnish)	0.0022%	45,386
Remaining individualsnot grpmax-eligible	0.0016%	62,500

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.Ala13Ser
Coding: c.37G>T
MANE Select: NM_144988
dbSNP: rs760001852
Type: single nucleotide variant
Location: chr1:95072862 (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

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

Similar variants

ALG14 p.Ala13Val Uncertain significance ★ ⚠ same residue
ALG14 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same condition
ALG14 p.Asn61Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Glu179Lys Uncertain significance ★★ ⚠ same condition
ALG14 p.Ile175Asn Uncertain significance ★★ ⚠ same condition
ALG14 p.Pro200Leu Uncertain significance ★★ ⚠ same condition
ALG14 p.Ser108Asn 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-ala13ser (accessed [today's date]).

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