Is FAS p.Asn326= (c.978C>T) pathogenic?

FAS p.Asn326= (c.978C>T) is classified Likely benign in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-05). Ultra-rare (popmax 0.0164%, mid); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Asn326= (c.978C>T)?

FAS p.Asn326= (c.978C>T) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Asn326= (c.978C>T) in the general population?

FAS p.Asn326= (c.978C>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.

FAS p.Asn326=

c.978C>T · rs768851846 · VCV1980680

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -0.34	GERP 1.2
Overall
CADD	0.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

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

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00316% 51/1,611,562 alleles · ultra-rare exomes 49/1,459,398 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.00398%	25,104

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.Asn326=
Coding: c.978C>T
MANE Select: NM_000043
dbSNP: rs768851846
Type: single nucleotide variant
Location: chr10:89014420 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB

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.Asn326Asp Uncertain significance ★★ ⚠ same residue
FAS p.Asn326His Uncertain significance ★ ⚠ same residue
FAS p.Asn326Thr Uncertain significance ★ ⚠ same residue
FAS p.Asn326Tyr 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

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-asn326 (accessed [today's date]).

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