Is FAS p.Pro64fs (c.191del) pathogenic?

FAS p.Pro64fs (c.191del) is classified Likely pathogenic in FAS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-08). Absent from gnomAD; Associated with FAS-related disorder.

What condition is associated with FAS p.Pro64fs (c.191del)?

FAS p.Pro64fs (c.191del) is associated with FAS-related disorder (ClinVar).

How common is FAS p.Pro64fs (c.191del) in the general population?

FAS p.Pro64fs (c.191del) is absent from gnomAD (gnomAD).

FAS p.Pro64fs

c.191del · rs1589465256 · VCV636739

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

FAS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.36	GERP 0.18, phastCons 0.13

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FAS
Protein: p.Pro64fs
Coding: c.191del
MANE Select: NM_000043
dbSNP: rs1589465256
Type: Deletion
Location: chr10:89003188 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB
Residue 64: a disulfide bond

Full FAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FAS-related disorder

Similar variants

FAS p.Lys193fs Likely pathogenic ★ same condition
FAS c.196+1G>A Pathogenic/Likely pathogenic ★★ same condition
FAS p.Arg250Gly Likely pathogenic ★★ same condition
FAS p.Cys135Tyr Likely pathogenic ★★ same condition
FAS p.Glu272Lys Pathogenic/Likely pathogenic ★★ same condition
FAS p.Arg121Trp Uncertain significance ★★ ⚠ same condition
FAS p.Thr163Ile Uncertain significance ★★ same condition
FAS c.569-1G>A 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-pro64fs (accessed [today's date]).

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