Is ALG14 p.Asn61Ser (c.182A>G) pathogenic?

ALG14 p.Asn61Ser (c.182A>G) is classified Uncertain significance in ALG14 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-06). AlphaMissense: likely benign (0.0599); Ultra-rare (popmax 0.075%, amr); Associated with intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies.

How common is ALG14 p.Asn61Ser (c.182A>G) in the general population?

ALG14 p.Asn61Ser (c.182A>G) is ultra-rare (popmax 0.075%, amr) (gnomAD).

What do computational predictors say about ALG14 p.Asn61Ser (c.182A>G)?

AlphaMissense predicts likely benign (score 0.0599) — an in-silico prediction, not a clinical call.

ALG14 p.Asn61Ser

Q: What condition is associated with ALG14 p.Asn61Ser (c.182A>G)?

ALG14 p.Asn61Ser (c.182A>G) is associated with intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies, congenital myasthenic syndrome 15, myopathy, epilepsy, and progressive cerebral atrophy (ClinVar).

c.182A>G · rs138996965 · VCV542122

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.075%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0599	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -4.42	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 -4	GERP -4.8
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	0.046	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 0.075% Admixed American · 45/60,000 alleles

Filtering AF 0.0625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.061%

Overall 0.0554% 894/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.075%	1,333
European (non-Finnish)	0.0665%	1,505
African / African-American	0.0626%	1,596
Remaining individualsnot grpmax-eligible	0.024%	4,165
South Asian	0.0022%	45,522
Finnishnot grpmax-eligible	0.00156%	63,998

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.Asn61Ser
Coding: c.182A>G
MANE Select: NM_144988
dbSNP: rs138996965
Type: single nucleotide variant
Location: chr1:95064972 (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

intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 15 myopathy, epilepsy, and progressive cerebral atrophy

Similar variants

ALG14 p.Asn61Asp Uncertain significance ★★ ⚠ same residue
ALG14 p.Ala13Ser Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
ALG14 p.Arg109Gln 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
ALG14 p.His190Gln 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-asn61ser (accessed [today's date]).

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