Is FARSB p.Ile237Phe (c.709A>T) pathogenic?

FARSB p.Ile237Phe (c.709A>T) is classified Uncertain significance in FARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely pathogenic (0.8582); Very rare (popmax 0.000493%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Ile237Phe (c.709A>T)?

FARSB p.Ile237Phe (c.709A>T) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Ile237Phe (c.709A>T) in the general population?

FARSB p.Ile237Phe (c.709A>T) is very rare (popmax 0.000493%, nfe) (gnomAD).

What do computational predictors say about FARSB p.Ile237Phe (c.709A>T)?

AlphaMissense predicts likely pathogenic (score 0.8582) — an in-silico prediction, not a clinical call.

FARSB p.Ile237Phe

c.709A>T · VCV4254880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000493%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8582	likely pathogenic
REVEL	0.688	pathogenic-leaning
SaProt	LLR -11.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 0.000493% European (non-Finnish) · 5/1,014,960 alleles

Filtering AF 0.000144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000105%

Overall 0.000349% 5/1,432,244 alleles · very rare

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: FARSB
Protein: p.Ile237Phe
Coding: c.709A>T
MANE Select: NM_005687
Type: single nucleotide variant
Location: chr2:222633205 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 237: a β-strand

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 p.Ile237Thr Uncertain significance ★ ⚠ same residue
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

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-ile237phe (accessed [today's date]).

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