Is AGL p.Ala714Val (c.2141C>T) pathogenic?

AGL p.Ala714Val (c.2141C>T) is classified Uncertain significance in AGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.0878); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGL p.Ala714Val (c.2141C>T)?

AGL p.Ala714Val (c.2141C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGL p.Ala714Val (c.2141C>T) in the general population?

AGL p.Ala714Val (c.2141C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AGL p.Ala714Val (c.2141C>T)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

AGL p.Ala714Val

c.2141C>T · VCV3506934

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -6.56	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	22.4	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 8.47e-05% European (non-Finnish) · 1/1,179,980 alleles

Overall 6.84e-05% 1/1,461,790 alleles · very rare

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: AGL
Protein: p.Ala714Val
Coding: c.2141C>T
MANE Select: NM_000642
Type: single nucleotide variant
Location: chr1:99881431 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 714: the 'amylo-1,6-glucosidase' region; an α-helix

Full AGL 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

Similar variants

AGL c.2681+1G>T Pathogenic/Likely pathogenic ★★ same condition
AGL p.Ala1128Thr Uncertain significance ★★ ⚠ same condition
AGL p.Ala1319Gly Uncertain significance ★★ ⚠ same condition
AGL p.Ala1404Thr Uncertain significance ★★ ⚠ same condition
AGL p.Ala396Val Uncertain significance ★★ ⚠ same condition
AGL p.Arg1000Cys Uncertain significance ★★ ⚠ same condition
AGL p.Arg1116His Uncertain significance ★★ ⚠ same condition
AGL p.Arg1151Trp 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/agl-p-ala714val (accessed [today's date]).

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