Is AGL p.Phe604Val (c.1810T>G) pathogenic?

AGL p.Phe604Val (c.1810T>G) is classified Conflicting classifications of pathogenicity in AGL (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-24). AlphaMissense: likely pathogenic (0.8553); Rare (popmax 0.393%, afr); Associated with Inborn genetic diseases.

What condition is associated with AGL p.Phe604Val (c.1810T>G)?

AGL p.Phe604Val (c.1810T>G) is associated with Inborn genetic diseases, glycogen storage disease III (ClinVar).

How common is AGL p.Phe604Val (c.1810T>G) in the general population?

AGL p.Phe604Val (c.1810T>G) is rare (popmax 0.393%, afr) (gnomAD).

What do computational predictors say about AGL p.Phe604Val (c.1810T>G)?

AlphaMissense predicts likely pathogenic (score 0.8553) — an in-silico prediction, not a clinical call.

AGL p.Phe604Val

c.1810T>G · rs138105395 · VCV456459

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8553 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.393%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8553	likely pathogenic
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -3.10	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.78 · regional, not allelic
Overall
CADD	26.1	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 0.393% African / African-American · 295/75,052 alleles

Filtering AF 0.356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.342%

Overall 0.0203% 328/1,614,066 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.393%	254
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.0183%	5,456
Middle Eastern	0.0165%	6,058
South Asian	0.00439%	22,770
European (non-Finnish)	0.000339%	294,986

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.Phe604Val
Coding: c.1810T>G
MANE Select: NM_000642
dbSNP: rs138105395
Type: single nucleotide variant
Location: chr1:99880706 (GRCh38)
Gene constraint: LOEUF 0.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 1 PDB
Residue 604: the 'amylo-1,6-glucosidase' region

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

Also linked: glycogen storage disease III

Similar variants

AGL c.1283+2T>C Likely pathogenic ★★ same condition
AGL c.1284-1G>A Likely pathogenic ★★ same condition
AGL c.1284-2A>G Likely pathogenic ★★ same condition
AGL c.1423+1G>A Pathogenic ★★ same condition
AGL c.1423+1G>C Pathogenic ★★ same condition
AGL c.1423+1G>T Pathogenic/Likely pathogenic ★★ same condition
AGL c.1612-1G>A Pathogenic/Likely pathogenic ★★ same condition
AGL c.1735+1G>T Pathogenic/Likely pathogenic ★★ 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-phe604val (accessed [today's date]).

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