Is FAS p.Leu2= (c.4C>T) pathogenic?

FAS p.Leu2= (c.4C>T) is classified Likely benign in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). Absent from gnomAD v4.1; Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Leu2= (c.4C>T)?

FAS p.Leu2= (c.4C>T) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Leu2= (c.4C>T) in the general population?

FAS p.Leu2= (c.4C>T) is absent from gnomAD v4.1 (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.Leu2=

c.4C>T · rs774656178 · VCV2114880

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -0.34	GERP 1.2
Overall
CADD	8.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FAS
Protein: p.Leu2=
Coding: c.4C>T
MANE Select: NM_001613 · reported on NM_000043
dbSNP: rs774656178
Type: single nucleotide variant
Location: chr10:88990880 (GRCh38)

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

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-leu2 (accessed [today's date]).

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