Is FARSB p.Asp488Glu (c.1464T>G) pathogenic?

FARSB p.Asp488Glu (c.1464T>G) is classified Uncertain significance in FARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). AlphaMissense: likely benign (0.2105); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Asp488Glu (c.1464T>G)?

FARSB p.Asp488Glu (c.1464T>G) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Asp488Glu (c.1464T>G) in the general population?

FARSB p.Asp488Glu (c.1464T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FARSB p.Asp488Glu (c.1464T>G)?

AlphaMissense predicts likely benign (score 0.2105) — an in-silico prediction, not a clinical call.

FARSB p.Asp488Glu

c.1464T>G · VCV3277731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2105	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -5.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.89	GERP -3.8, phastCons 0.97
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	16.46	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: FARSB
Protein: p.Asp488Glu
Coding: c.1464T>G
MANE Select: NM_005687
Type: single nucleotide variant
Location: chr2:222600082 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FARSB c.716-3C>T Uncertain significance ★★ same condition
FARSB p.Ala287Gly Uncertain significance ★★ ⚠ same condition
FARSB p.Arg127Cys Uncertain significance ★★ ⚠ same condition
FARSB p.Arg127His Uncertain significance ★★ ⚠ same condition
FARSB p.Arg135Leu Uncertain significance ★★ ⚠ same condition
FARSB p.Arg466Cys Uncertain significance ★★ ⚠ same condition
FARSB p.Arg98Trp Uncertain significance ★★ ⚠ same condition
FARSB p.Asn205Ser Uncertain significance ★★ ⚠ 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/farsb-p-asp488glu (accessed [today's date]).

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