Is FAS p.Ala290= (c.870G>A) pathogenic?

FAS p.Ala290= (c.870G>A) is classified Likely benign in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). Ultra-rare (popmax 0.0134%, eas); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Ala290= (c.870G>A)?

FAS p.Ala290= (c.870G>A) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Ala290= (c.870G>A) in the general population?

FAS p.Ala290= (c.870G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Autoimmune lymphoproliferative syndrome inherited?

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

FAS p.Ala290=

c.870G>A · rs370426812 · VCV2194172

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

autoimmune lymphoproliferative syndrome type 1

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 -1.7	GERP -2.5
Overall
CADD	0.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,858 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.0031% 50/1,613,758 alleles · ultra-rare exomes 45/1,461,632 · genomes 5/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,476
Finnishnot grpmax-eligible	0.00782%	12,791
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00401%	24,964
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
European (non-Finnish)	0.00229%	43,701

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.Ala290=
Coding: c.870G>A
MANE Select: NM_000043
dbSNP: rs370426812
Type: single nucleotide variant
Location: chr10:89014312 (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.Ala290Val Uncertain significance ★ 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-ala290 (accessed [today's date]).

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