Is FAR1 p.Leu499fs (c.1494del) pathogenic?

FAR1 p.Leu499fs (c.1494del) is classified Uncertain significance in FAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). No gnomAD frequency available for this variant.

How common is FAR1 p.Leu499fs (c.1494del) in the general population?

FAR1 p.Leu499fs (c.1494del) is no gnomAD frequency available for this variant (gnomAD).

FAR1 p.Leu499fs

c.1494del · rs2134204262 · VCV1468135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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: FAR1
Protein: p.Leu499fs
Coding: c.1494del
MANE Select: NM_032228
dbSNP: rs2134204262
Type: Deletion
Location: chr11:13728720 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 499: the 'necessary and sufficient for pex19-mediated localization into peroxisome membrane' region; a UniProt-annotated variant site (in pfcrd; results in a complete loss of enzyme activity)

Full FAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAR1 p.Leu499= Likely benign ★ same residue
FAR1 c.1257+16_1257+17del Likely benign ★★ same type
FAR1 c.365+9_365+10del Likely benign ★★ same type
FAR1 p.Lys78fs Pathogenic ★ same type
FAR1 c.1257+8_1257+11del Likely benign ★ same type
FAR1 c.1258-11del Likely benign ★ same type
FAR1 c.1385+12_1385+19del Likely benign ★ same type
FAR1 c.365+19_365+25del Likely benign ★ same type

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/far1-p-leu499fs (accessed [today's date]).

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