Is FAS p.Lys61= (c.183G>A) pathogenic?

FAS p.Lys61= (c.183G>A) is classified Benign/Likely benign in FAS (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-07-01). Low-frequency (popmax 1.08%, nfe); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Lys61= (c.183G>A)?

FAS p.Lys61= (c.183G>A) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Lys61= (c.183G>A) in the general population?

FAS p.Lys61= (c.183G>A) is low-frequency (popmax 1.08%, nfe) (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.Lys61=

c.183G>A · rs3218613 · VCV155871

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.03	GERP -2.5
Overall
CADD	0.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% European (non-Finnish) · 12,777/1,179,948 alleles

Filtering AF 1.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.902% 14,563/1,614,074 alleles · low-frequency exomes 13,653/1,461,780 · genomes 910/152,294 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.08%	92
South Asian	0.831%	120
Remaining individualsnot grpmax-eligible	0.722%	139
Finnishnot grpmax-eligible	0.558%	179
Middle Eastern	0.247%	404
Admixed American	0.157%	638
African / African-American	0.135%	743
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
East Asian	0.00668%	14,962

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.Lys61=
Coding: c.183G>A
MANE Select: NM_000043
dbSNP: rs3218613
Type: single nucleotide variant
Location: chr10:89003181 (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.Lys61fs Pathogenic ★ 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-lys61 (accessed [today's date]).

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