Is FAS p.Gln47Arg (c.140A>G) pathogenic?

FAS p.Gln47Arg (c.140A>G) is classified Conflicting classifications of pathogenicity in FAS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0688); Ultra-rare (popmax 0.0955%, sas); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Gln47Arg (c.140A>G)?

FAS p.Gln47Arg (c.140A>G) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Gln47Arg (c.140A>G) in the general population?

FAS p.Gln47Arg (c.140A>G) is ultra-rare (popmax 0.0955%, sas) (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.Gln47Arg (c.140A>G)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

FAS p.Gln47Arg

c.140A>G · rs553156945 · VCV2081225

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0955%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune lymphoproliferative syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.123	moderately benign-leaning
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.8
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.16 · regional, not allelic
Overall
CADD	0.032	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 0.0955% South Asian · 87/91,086 alleles

Filtering AF 0.0793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0733%

Overall 0.00576% 93/1,614,212 alleles · ultra-rare exomes 87/1,461,852 · genomes 6/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0955%	1,047
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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.Gln47Arg
Coding: c.140A>G
MANE Select: NM_000043
dbSNP: rs553156945
Type: single nucleotide variant
Location: chr10:89003138 (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.Gln47= 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
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-gln47arg (accessed [today's date]).

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