Is FAR1 p.Ser498= (c.1494T>C) pathogenic?

FAR1 p.Ser498= (c.1494T>C) is classified Likely benign in FAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). Very rare (popmax 0.00017%, nfe).

How common is FAR1 p.Ser498= (c.1494T>C) in the general population?

FAR1 p.Ser498= (c.1494T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

FAR1 p.Ser498=

c.1494T>C · rs2500170646 · VCV2108014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 0.69, phastCons 1
Overall
CADD	11.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,746 alleles

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

Overall 0.000186% 3/1,612,446 alleles · very rare exomes 3/1,460,432 · genomes 0/152,014 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)grpmax	0.00017%	589,372

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FAR1
Protein: p.Ser498=
Coding: c.1494T>C
MANE Select: NM_032228
dbSNP: rs2500170646
Type: single nucleotide variant
Location: chr11:13728720 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.57 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 498: 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.Ser498Asn Uncertain significance ★★ ⚠ same residue
FAR1 c.-7-2A>G Likely pathogenic ★★ same type
FAR1 p.Arg480Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
FAR1 p.Arg480His Pathogenic/Likely pathogenic ★★ same type
FAR1 p.Arg480Leu Pathogenic ★★ same type
FAR1 c.546-13A>G Uncertain significance ★★ same type
FAR1 p.Ala361Val Uncertain significance ★★ ⚠ same type
FAR1 p.Arg133Gln Uncertain significance ★★ ⚠ 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-ser498 (accessed [today's date]).

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