Is FARSB p.Cys76Arg (c.226T>C) pathogenic?

FARSB p.Cys76Arg (c.226T>C) is classified Pathogenic in FARSB (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9926); Very rare (popmax 0.00305%, nfe); Associated with Cerebral calcification.

What condition is associated with FARSB p.Cys76Arg (c.226T>C)?

FARSB p.Cys76Arg (c.226T>C) is associated with Cerebral calcification, cirrhosis of liver (ClinVar).

How common is FARSB p.Cys76Arg (c.226T>C) in the general population?

FARSB p.Cys76Arg (c.226T>C) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about FARSB p.Cys76Arg (c.226T>C)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

FARSB p.Cys76Arg

c.226T>C · rs1419129874 · VCV545695

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cerebral calcification

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic ✓ concordant with ClinVar · top 2% in FARSB
REVEL	0.981	strongly pathogenic-leaning
SaProt	LLR -17.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	31.0	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 0.00305% European (non-Finnish) · 36/1,179,250 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00223% 36/1,612,986 alleles · very rare exomes 35/1,460,754 · genomes 1/152,232 · joint denominator

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.Cys76Arg
Coding: c.226T>C
MANE Select: NM_005687
dbSNP: rs1419129874
Type: single nucleotide variant
Location: chr2:222642894 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 76: a UniProt-annotated variant site (in rildbc1)

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

Disease context

Cerebral calcification — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cirrhosis of liver

Similar variants

FARSB p.Arg401Gln Pathogenic ★ same condition
FARSB p.Lys262Glu Pathogenic ★ same condition
FARSB p.Thr461Pro Pathogenic ★ same condition
FARSB p.Phe252Ser Pathogenic same condition
FARSB c.848+1G>A Pathogenic/Likely pathogenic ★★ same type
FARSB p.Glu285Lys Pathogenic/Likely pathogenic ★★ same type
FARSB c.716-3C>T Uncertain significance ★★ same type
FARSB p.Ala287Gly 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/farsb-p-cys76arg (accessed [today's date]).

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