Is FARSB p.Pro94Ser (c.280C>T) pathogenic?

FARSB p.Pro94Ser (c.280C>T) is classified Uncertain significance in FARSB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-15). AlphaMissense: ambiguous (0.5356); Ultra-rare (popmax 0.0182%, afr); Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Pro94Ser (c.280C>T)?

FARSB p.Pro94Ser (c.280C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Pro94Ser (c.280C>T) in the general population?

FARSB p.Pro94Ser (c.280C>T) is ultra-rare (popmax 0.0182%, afr) (gnomAD).

What do computational predictors say about FARSB p.Pro94Ser (c.280C>T)?

AlphaMissense predicts ambiguous (score 0.5356) — an in-silico prediction, not a clinical call.

FARSB p.Pro94Ser

c.280C>T · rs139430746 · VCV2190884

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5356	ambiguous
REVEL	0.652	pathogenic-leaning
SaProt	LLR -11.29	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% African / African-American · 13/71,334 alleles

Filtering AF 0.0107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0085%

Overall 0.00147% 22/1,498,604 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0182%	5,487
Admixed American	0.0131%	7,631
South Asian	0.00121%	82,946
European (non-Finnish)	9.16e-05%	1,091,257

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.Pro94Ser
Coding: c.280C>T
MANE Select: NM_005687
dbSNP: rs139430746
Type: single nucleotide variant
Location: chr2:222640921 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 94: 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-pro94ser (accessed [today's date]).

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