Is FXN p.Ser17Ile (c.50G>T) pathogenic?

FXN p.Ser17Ile (c.50G>T) is classified Uncertain significance in FXN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: likely benign (0.1298); Very rare (popmax 0.00044%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FXN p.Ser17Ile (c.50G>T)?

FXN p.Ser17Ile (c.50G>T) is associated with Inborn genetic diseases (ClinVar).

How common is FXN p.Ser17Ile (c.50G>T) in the general population?

FXN p.Ser17Ile (c.50G>T) is very rare (popmax 0.00044%, nfe) (gnomAD).

What do computational predictors say about FXN p.Ser17Ile (c.50G>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

FXN p.Ser17Ile

c.50G>T · rs1831536874 · VCV3097551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00044%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -8.45	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 0.52	GERP -1.3
Regional constraint	o/e 0.99	unconstrained · MANE · 37 kb · p 0.93 · regional, not allelic
Overall
CADD	14.14	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 0.00044% European (non-Finnish) · 5/1,137,640 alleles

Filtering AF 0.000129% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.00033% 5/1,513,248 alleles · very rare exomes 5/1,361,040 · genomes 0/152,208 · 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: FXN
Protein: p.Ser17Ile
Coding: c.50G>T
MANE Select: NM_000144
dbSNP: rs1831536874
Type: single nucleotide variant
Location: chr9:69035832 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 75.93 · 19 PDB

Full FXN 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

FXN p.Arg43His Uncertain significance ★★ ⚠ same condition
FXN p.Gly138Arg Uncertain significance ★★ ⚠ same condition
FXN p.Leu24Phe Uncertain significance ★★ ⚠ same condition
FXN p.Pro30Thr Uncertain significance ★★ ⚠ same condition
FXN p.Thr49Asn Uncertain significance ★★ ⚠ same condition
FXN p.Arg54= Benign/Likely benign ★★ same condition
FXN p.Asp178= Benign/Likely benign ★★ same condition
FXN p.Asp209Gly Benign/Likely benign ★★ 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/fxn-p-ser17ile (accessed [today's date]).

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