Is FAS p.Val83= (c.249G>A) pathogenic?

FAS p.Val83= (c.249G>A) is classified Likely benign in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). Very rare (popmax 0.00833%, amr); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Val83= (c.249G>A)?

FAS p.Val83= (c.249G>A) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Val83= (c.249G>A) in the general population?

FAS p.Val83= (c.249G>A) is very rare (popmax 0.00833%, amr) (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.Val83=

c.249G>A · rs771050216 · VCV2172165

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

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 -0.54	GERP -1.6
Overall
CADD	2.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,992 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000479% 7/1,461,758 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,998
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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.Val83=
Coding: c.249G>A
MANE Select: NM_000043
dbSNP: rs771050216
Type: single nucleotide variant
Location: chr10:89007752 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB
Residue 83: a β-strand

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.Val83Met 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
FAS p.Cys135Tyr 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-val83 (accessed [today's date]).

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