Is GAA p.Phe649fs (c.1944_1946delinsAA) pathogenic?

GAA p.Phe649fs (c.19441946delinsAA) is classified Likely pathogenic in GAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). No gnomAD frequency available for this variant.

How common is GAA p.Phe649fs (c.1944_1946delinsAA) in the general population?

GAA p.Phe649fs (c.1944_1946delinsAA) is no gnomAD frequency available for this variant (gnomAD).

GAA p.Phe649fs

c.1944_1946delinsAA · rs2510383585 · VCV2690603

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -0.43, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GAA
Protein: p.Phe649fs
Coding: c.1944_1946delinsAA
MANE Select: NM_000152
dbSNP: rs2510383585
Type: Indel
Location: chr17:80112931 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.32 · 19 PDB
Residue 649: a β-strand

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

Similar variants

GAA p.Phe649= Conflicting classifications of pathogenicity ★ same residue
GAA p.Phe649Leu Uncertain significance ★ ⚠ same residue
GAA p.Phe649Ile Uncertain significance ⚠ same residue
GAA p.Ala761fs Pathogenic ★★★ same type
GAA p.Asn535fs Likely pathogenic ★★★ same type
GAA p.Ser529Val Likely pathogenic ★★★ same type
GAA p.Trp376fs Pathogenic ★★★ same type
GAA p.Tyr256fs Pathogenic ★★★ same type

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-phe649fs (accessed [today's date]).

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