Is AAAS p.Phe464fs (c.1389del) pathogenic?

AAAS p.Phe464fs (c.1389del) is classified Pathogenic in AAAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Absent from gnomAD.

How common is AAAS p.Phe464fs (c.1389del) in the general population?

AAAS p.Phe464fs (c.1389del) is absent from gnomAD (gnomAD).

AAAS p.Phe464fs

c.1389del · rs2121080959 · VCV3771174

Pathogenic Single submitter

Classification

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (15 of 16, 27 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, 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: AAAS
Protein: p.Phe464fs
Coding: c.1389del
MANE Select: NM_015665
dbSNP: rs2121080959
Type: Deletion
Location: chr12:53307872 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45 · 2 PDB
Residue 464: a UniProt-annotated variant site (in aaas); a UniProt-annotated variant site (in aaas; uncertain significance)

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

Similar variants

AAAS p.Arg258fs Pathogenic ★★ same type
AAAS p.Gln456fs Pathogenic/Likely pathogenic ★★ same type
AAAS p.His71fs Pathogenic/Likely pathogenic ★★ same type
AAAS p.Leu356fs Pathogenic ★★ same type
AAAS p.Ser255fs Pathogenic/Likely pathogenic ★★ same type
AAAS p.Tyr19_Glu20delinsTer Pathogenic ★★ same type
AAAS c.310_317delTTTGAGTG Pathogenic ★ same type
AAAS p.Arg85fs 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/aaas-p-phe464fs (accessed [today's date]).

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