Is ALG14 p.Ser60Cys (c.179C>G) pathogenic?

ALG14 p.Ser60Cys (c.179C>G) is classified Uncertain significance in ALG14 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1824); Ultra-rare (popmax 0.0713%, eas); Associated with myopathy, epilepsy, and progressive cerebral atrophy.

What condition is associated with ALG14 p.Ser60Cys (c.179C>G)?

ALG14 p.Ser60Cys (c.179C>G) 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.Ser60Cys (c.179C>G) in the general population?

ALG14 p.Ser60Cys (c.179C>G) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about ALG14 p.Ser60Cys (c.179C>G)?

AlphaMissense predicts likely benign (score 0.1824) — an in-silico prediction, not a clinical call.

ALG14 p.Ser60Cys

c.179C>G · rs780277809 · VCV390702

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1824 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

myopathy, epilepsy, and progressive cerebral atrophy

Computational evidence

Protein change
AlphaMissense	0.1824	likely benign
REVEL	0.594	indeterminate
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	27.4	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 0.0713% East Asian · 32/44,862 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00477% 77/1,613,454 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,402
Remaining individualsnot grpmax-eligible	0.0464%	2,154
Admixed American	0.0233%	4,285
European (non-Finnish)	0.00017%	589,831

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.Ser60Cys
Coding: c.179C>G
MANE Select: NM_144988
dbSNP: rs780277809
Type: single nucleotide variant
Location: chr1:95064975 (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

Also linked: congenital myasthenic syndrome 15 intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies

Similar variants

ALG14 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
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-ser60cys (accessed [today's date]).

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