Is FAS p.Ala237= (c.711T>C) pathogenic?

FAS p.Ala237= (c.711T>C) is classified Likely benign in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-26). Very rare (popmax 0.00186%, nfe); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Ala237= (c.711T>C)?

FAS p.Ala237= (c.711T>C) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Ala237= (c.711T>C) in the general population?

FAS p.Ala237= (c.711T>C) is very rare (popmax 0.00186%, 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.Ala237=

c.711T>C · rs1272633083 · VCV2117217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

autoimmune lymphoproliferative syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.027	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.045	GERP 1.4, phastCons 0.93
Overall
CADD	3.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,904 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,730 alleles · very rare

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.Ala237=
Coding: c.711T>C
MANE Select: NM_000043
dbSNP: rs1272633083
Type: single nucleotide variant
Location: chr10:89014153 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB
Residue 237: the 'interaction with calm' region; the death domain; the 'interaction with hipk3' region; an α-helix

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 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
FAS p.Glu272Lys Pathogenic/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-ala237 (accessed [today's date]).

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