Is FAR1 p.Ser505Pro (c.1513T>C) pathogenic?

FAR1 p.Ser505Pro (c.1513T>C) is classified Uncertain significance in FAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely pathogenic (0.7105); Absent from gnomAD v4.1; Associated with spastic paraparesis-cataracts-speech delay syndrome.

What condition is associated with FAR1 p.Ser505Pro (c.1513T>C)?

FAR1 p.Ser505Pro (c.1513T>C) is associated with spastic paraparesis-cataracts-speech delay syndrome (ClinVar).

How common is FAR1 p.Ser505Pro (c.1513T>C) in the general population?

FAR1 p.Ser505Pro (c.1513T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FAR1 p.Ser505Pro (c.1513T>C)?

AlphaMissense predicts likely pathogenic (score 0.7105) — an in-silico prediction, not a clinical call.

FAR1 p.Ser505Pro

c.1513T>C · VCV4292257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

spastic paraparesis-cataracts-speech delay syndrome

Computational evidence

Protein change
AlphaMissense	0.7105	likely pathogenic
REVEL	0.471	indeterminate
SaProt	LLR -12.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 139 bp · p 3.3e-08 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FAR1
Protein: p.Ser505Pro
Coding: c.1513T>C
MANE Select: NM_032228
Type: single nucleotide variant
Location: chr11:13728739 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 505: 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

Disease context

spastic paraparesis-cataracts-speech delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FAR1 p.Arg480Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
FAR1 p.Arg480His Pathogenic/Likely pathogenic ★★ same condition
FAR1 p.Arg480Leu Pathogenic ★★ same condition
FAR1 p.Tyr303= Benign/Likely benign ★★ same condition
FAR1 p.Arg480Ser Likely pathogenic ★ same condition
FAR1 p.Arg508Ter Likely pathogenic ★ same condition
FAR1 p.Trp493Cys Uncertain significance ★ ⚠ same condition
FAR1 c.-7-2A>G Likely pathogenic ★★ 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-ser505pro (accessed [today's date]).

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