Is FARSB p.Phe12Ser (c.35T>C) pathogenic?

FARSB p.Phe12Ser (c.35T>C) is classified Uncertain significance in FARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely pathogenic (0.6759); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Phe12Ser (c.35T>C)?

FARSB p.Phe12Ser (c.35T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Phe12Ser (c.35T>C) in the general population?

FARSB p.Phe12Ser (c.35T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FARSB p.Phe12Ser (c.35T>C)?

AlphaMissense predicts likely pathogenic (score 0.6759) — an in-silico prediction, not a clinical call.

FARSB p.Phe12Ser

c.35T>C · rs2469469659 · VCV2261413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6759	likely pathogenic
REVEL	0.334	indeterminate
SaProt	LLR -12.39	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 11	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	29.5	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: FARSB
Protein: p.Phe12Ser
Coding: c.35T>C
MANE Select: NM_005687
dbSNP: rs2469469659
Type: single nucleotide variant
Location: chr2:222656039 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 12: an α-helix

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-phe12ser (accessed [today's date]).

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