Is FAS p.Leu7Pro (c.20T>C) pathogenic?

FAS p.Leu7Pro (c.20T>C) is classified Likely pathogenic in FAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-20). AlphaMissense: likely benign (0.2448); Very rare (popmax 0.000169%, nfe); Associated with autoimmune lymphoproliferative syndrome type 1.

What condition is associated with FAS p.Leu7Pro (c.20T>C)?

FAS p.Leu7Pro (c.20T>C) is associated with autoimmune lymphoproliferative syndrome type 1 (ClinVar).

How common is FAS p.Leu7Pro (c.20T>C) in the general population?

FAS p.Leu7Pro (c.20T>C) is very rare (popmax 0.000169%, nfe) (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.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely benign (score 0.2448) — an in-silico prediction, not a clinical call.

FAS p.Leu7Pro

c.20T>C · rs2133384423 · VCV1213255

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autoimmune lymphoproliferative syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.2448	likely benign ⚠ discordant with ClinVar
REVEL	0.572	indeterminate
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.4	GERP 1.2
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.16 · regional, not allelic
Overall
CADD	19.58	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 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,886 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.Leu7Pro
Coding: c.20T>C
MANE Select: NM_001613 · reported on NM_000043
dbSNP: rs2133384423
Type: single nucleotide variant
Location: chr10:88990896 (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-leu7pro (accessed [today's date]).

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