Is FARSB p.Ile341Thr (c.1022T>C) pathogenic?

FARSB p.Ile341Thr (c.1022T>C) is classified Uncertain significance in FARSB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0468); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with FARSB p.Ile341Thr (c.1022T>C)?

FARSB p.Ile341Thr (c.1022T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FARSB p.Ile341Thr (c.1022T>C) in the general population?

FARSB p.Ile341Thr (c.1022T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about FARSB p.Ile341Thr (c.1022T>C)?

AlphaMissense predicts likely benign (score 0.0468) — an in-silico prediction, not a clinical call.

FARSB p.Ile341Thr

c.1022T>C · VCV4619660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0468 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0468	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.88	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 6.9	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 84 kb · p 0.00072 · regional, not allelic
Overall
CADD	18.12	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0165% Middle Eastern · 1/6,054 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00217% 35/1,613,412 alleles · ultra-rare exomes 33/1,461,138 · genomes 2/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0048%	20,831
South Asian	0.00439%	22,767
African / African-American	0.00267%	37,510
East Asian	0.00223%	44,864
European (non-Finnish)	0.00195%	51,278
Finnishnot grpmax-eligible	0.00156%	64,020

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.Ile341Thr
Coding: c.1022T>C
MANE Select: NM_005687
Type: single nucleotide variant
Location: chr2:222624420 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.71 · 3 PDB
Residue 341: the b5 domain

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-ile341thr (accessed [today's date]).

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