Is FARSB p.Val558Ile (c.1672G>A) pathogenic?

FARSB p.Val558Ile (c.1672G>A) is classified Likely benign in FARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.0684); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Val558Ile (c.1672G>A)?

FARSB p.Val558Ile (c.1672G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Val558Ile (c.1672G>A) in the general population?

FARSB p.Val558Ile (c.1672G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about FARSB p.Val558Ile (c.1672G>A)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

FARSB p.Val558Ile

c.1672G>A · rs776755911 · VCV2593802

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -4.2
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	0.2	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 0.0022% South Asian · 2/91,074 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00192% 31/1,613,804 alleles · very rare exomes 27/1,461,726 · genomes 4/152,078 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0125%	8,001
South Asiangrpmax	0.0022%	45,537
European (non-Finnish)	0.00161%	62,101
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00134%	74,888

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val558Ile
Coding: c.1672G>A
MANE Select: NM_005687
dbSNP: rs776755911
Type: single nucleotide variant
Location: chr2:222571969 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 558: 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.Val558= Likely benign ★ 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-val558ile (accessed [today's date]).

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