Is FARSB p.Phe252Ser (c.755T>C) pathogenic?

FARSB p.Phe252Ser (c.755T>C) is classified Pathogenic in FARSB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-09-08). AlphaMissense: likely pathogenic (0.9675); Very rare (popmax 8.74e-05%, nfe); Associated with Rajab interstitial lung disease with brain calcifications.

What condition is associated with FARSB p.Phe252Ser (c.755T>C)?

FARSB p.Phe252Ser (c.755T>C) is associated with Rajab interstitial lung disease with brain calcifications, cirrhosis of liver (ClinVar).

How common is FARSB p.Phe252Ser (c.755T>C) in the general population?

FARSB p.Phe252Ser (c.755T>C) is very rare (popmax 8.74e-05%, nfe) (gnomAD).

What do computational predictors say about FARSB p.Phe252Ser (c.755T>C)?

AlphaMissense predicts likely pathogenic (score 0.9675) — an in-silico prediction, not a clinical call.

FARSB p.Phe252Ser

c.755T>C · rs1466642025 · VCV545694

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.74e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Rajab interstitial lung disease with brain calcifications

Computational evidence

Protein change
AlphaMissense	0.9675	likely pathogenic ✓ concordant with ClinVar · top 9% in FARSB
REVEL	0.686	pathogenic-leaning
SaProt	LLR -16.02	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 11	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	27.2	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 8.74e-05% European (non-Finnish) · 1/1,143,634 alleles

Overall 6.36e-05% 1/1,573,490 alleles · very rare exomes 0/1,421,254 · genomes 1/152,236 · 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.Phe252Ser
Coding: c.755T>C
MANE Select: NM_005687
dbSNP: rs1466642025
Type: single nucleotide variant
Location: chr2:222631635 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 252: a β-strand; a UniProt-annotated variant site (in rildbc1)

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

Disease context

Rajab interstitial lung disease with brain calcifications — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cirrhosis of liver

Similar variants

FARSB c.848+1G>A Pathogenic/Likely pathogenic ★★ same condition
FARSB p.Glu285Lys Pathogenic/Likely pathogenic ★★ same condition
FARSB p.Arg305Gln Likely pathogenic ★ ⚠ same condition
FARSB p.Arg401Gln Pathogenic ★ same condition
FARSB p.Cys76Arg Pathogenic ★ same condition
FARSB p.Lys262Glu Pathogenic ★ same condition
FARSB p.Thr461Pro Pathogenic ★ same condition
FARSB p.Thr256Met 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-phe252ser (accessed [today's date]).

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