Is FAS p.Ala290fs (c.868_871delinsTCA) pathogenic?

FAS p.Ala290fs (c.868871delinsTCA) is classified Likely pathogenic in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01).

FAS p.Ala290fs

c.868_871delinsTCA · VCV4535435

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: FAS
Protein: p.Ala290fs
Coding: c.868_871delinsTCA
MANE Select: NM_000043
Type: Indel
Location: chr10:89014310 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB
Residue 290: the death domain; the 'interaction with hipk3' region; an α-helix

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

Similar variants

FAS p.Ala290Glu Uncertain significance ★ ⚠ same residue
FAS p.Ala290Val Uncertain significance ★ same residue
FAS p.Ala290= Likely benign ★ same residue
FAS p.Phe133fs Pathogenic ★ same type
FAS p.Thr241_Ser243delinsLeuGluSerCys Likely pathogenic ★ same type
FAS p.Thr214Asn Uncertain significance ★ same type
FAS p.Thr214Ile Uncertain significance ★ same type
FAS p.Trp189_Val190delinsTyrLysAsnLeu Uncertain significance ★ 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/fas-p-ala290fs (accessed [today's date]).

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