Is AGA p.Ala101= (c.303A>T) pathogenic?

AGA p.Ala101= (c.303A>T) is classified Benign/Likely benign in AGA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Rare (popmax 0.529%, afr); Associated with Inborn genetic diseases.

What condition is associated with AGA p.Ala101= (c.303A>T)?

AGA p.Ala101= (c.303A>T) is associated with Inborn genetic diseases, aspartylglucosaminuria (ClinVar).

How common is AGA p.Ala101= (c.303A>T) in the general population?

AGA p.Ala101= (c.303A>T) is rare (popmax 0.529%, afr) (gnomAD).

AGA p.Ala101=

c.303A>T · rs142449515 · VCV254724

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.529%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -2.5, phastCons 0.55
Overall
CADD	8.474	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.529% African / African-American · 397/75,044 alleles

Filtering AF 0.486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.027% 435/1,613,590 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.529%	189
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.0233%	4,287
European (non-Finnish)	0.00017%	589,748

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: AGA
Protein: p.Ala101=
Coding: c.303A>T
MANE Select: NM_000027
dbSNP: rs142449515
Type: single nucleotide variant
Location: chr4:177439667 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.41 · 2 PDB
Residue 101: a UniProt-annotated variant site (in agu); a β-strand

Full AGA 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: aspartylglucosaminuria

Similar variants

AGA p.Ala101Val Pathogenic/Likely pathogenic ★★ same residue
AGA p.Ala101Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
AGA c.127+1G>A Likely pathogenic ★★ same condition
AGA c.127+1G>T Likely pathogenic ★★ same condition
AGA c.128-2A>G Pathogenic ★★ same condition
AGA c.281+1G>T Likely pathogenic ★★ same condition
AGA c.395-8A>G Pathogenic/Likely pathogenic ★★ same condition
AGA c.508-2A>C 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/aga-p-ala101 (accessed [today's date]).

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