Is FAS p.Ala290Val (c.869C>T) pathogenic?

FAS p.Ala290Val (c.869C>T) is classified Uncertain significance in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: ambiguous (0.5587); Ultra-rare (popmax 0.0164%, mid); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Ala290Val (c.869C>T)?

FAS p.Ala290Val (c.869C>T) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Ala290Val (c.869C>T) in the general population?

FAS p.Ala290Val (c.869C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Autoimmune lymphoproliferative syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FAS p.Ala290Val (c.869C>T)?

AlphaMissense predicts ambiguous (score 0.5587) — an in-silico prediction, not a clinical call.

FAS p.Ala290Val

c.869C>T · rs760993872 · VCV2961796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

autoimmune lymphoproliferative syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.5587	ambiguous
REVEL	0.453	indeterminate
SaProt	LLR -6.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 143 bp · p 0.92 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,613,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Finnishnot grpmax-eligible	0.00156%	63,948
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000339%	294,979

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: FAS
Protein: p.Ala290Val
Coding: c.869C>T
MANE Select: NM_000043
dbSNP: rs760993872
Type: single nucleotide variant
Location: chr10:89014311 (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

Disease context

autoimmune lymphoproliferative syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune lymphoproliferative syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

FAS p.Ala290Glu Uncertain significance ★ ⚠ same residue
FAS p.Ala290= Likely benign ★ same residue
FAS c.651+1G>A Pathogenic/Likely pathogenic ★★ same condition
FAS c.651+2T>C Pathogenic ★★ same condition
FAS p.Arg250Gln Pathogenic/Likely pathogenic ★★ same condition
FAS p.Arg250Gly Likely pathogenic ★★ same condition
FAS p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
FAS p.Asp260Asn 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/fas-p-ala290val (accessed [today's date]).

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