Is ALG14 p.Arg88Gln (c.263G>A) pathogenic?

ALG14 p.Arg88Gln (c.263G>A) is classified Uncertain significance in ALG14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.1078); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with ALG14 p.Arg88Gln (c.263G>A)?

ALG14 p.Arg88Gln (c.263G>A) is associated with Inborn genetic diseases, congenital myasthenic syndrome 15 (ClinVar).

How common is ALG14 p.Arg88Gln (c.263G>A) in the general population?

ALG14 p.Arg88Gln (c.263G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ALG14 p.Arg88Gln (c.263G>A)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

ALG14 p.Arg88Gln

c.263G>A · rs768365586 · VCV2034246

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP 0.17, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 90 kb · p 0.32 · regional, not allelic
Overall
CADD	19.18	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 0.00334% Admixed American · 2/59,966 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00155% 25/1,613,512 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,983
Remaining individualsnot grpmax-eligible	0.0032%	31,227
East Asian	0.00223%	44,888
European (non-Finnish)	0.00153%	65,540
African / African-American	0.00134%	74,906
South Asian	0.0011%	91,030

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.Arg88Gln
Coding: c.263G>A
dbSNP: rs768365586
Type: single nucleotide variant
Location: chr1:95064891 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 15

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-arg88gln (accessed [today's date]).

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