Is GAA p.Phe90= (c.270C>T) pathogenic?

GAA p.Phe90= (c.270C>T) is classified Likely benign in GAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0357%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GAA p.Phe90= (c.270C>T)?

GAA p.Phe90= (c.270C>T) is associated with Cardiovascular phenotype, glycogen storage disease II (ClinVar).

How common is GAA p.Phe90= (c.270C>T) in the general population?

GAA p.Phe90= (c.270C>T) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

GAA p.Phe90=

c.270C>T · rs768078324 · VCV456413

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Conditions

Cardiovascular phenotype

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 -3.8	GERP -2.7
Overall
CADD	4.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% East Asian · 16/44,858 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00267% 43/1,612,836 alleles · ultra-rare exomes 41/1,460,616 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,804
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)	0.00203%	49,165
African / African-American	0.00133%	74,928

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: GAA
Protein: p.Phe90=
Coding: c.270C>T
MANE Select: NM_000152
dbSNP: rs768078324
Type: single nucleotide variant
Location: chr17:80104856 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 90: the p-type domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease II

Similar variants

GAA p.Phe90Ile Uncertain significance ★★ ⚠ same residue
GAA c.1076-1G>C Pathogenic ★★★ same condition
GAA c.1076-22T>G Pathogenic ★★★ same condition
GAA c.1194+5G>A Likely pathogenic ★★★ same condition
GAA c.1326+1G>A Pathogenic ★★★ same condition
GAA c.1327-2A>G Pathogenic ★★★ same condition
GAA c.1437+1G>A Likely pathogenic ★★★ same condition
GAA c.1437+2T>C 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/gaa-p-phe90 (accessed [today's date]).

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