Is FXN p.Ala31= (c.93A>C) pathogenic?

FXN p.Ala31= (c.93A>C) is classified Likely benign in FXN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Ultra-rare (popmax 0.0268%, mid).

How common is FXN p.Ala31= (c.93A>C) in the general population?

FXN p.Ala31= (c.93A>C) is ultra-rare (popmax 0.0268%, mid) (gnomAD).

FXN p.Ala31=

c.93A>C · rs2133086878 · VCV3250670

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0268%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -1.4
Overall
CADD	6.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0268% Middle Eastern · 1/3,736 alleles

Filtering AF 0.0065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00312% 43/1,380,292 alleles · ultra-rare exomes 42/1,231,942 · genomes 1/148,350 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.028%	3,569
Middle Easterngrpmax	0.0268%	3,736
Ashkenazi Jewishnot grpmax-eligible	0.017%	5,895
East Asian	0.0167%	6,002
Admixed American	0.00687%	14,553
Remaining individualsnot grpmax-eligible	0.00587%	17,042
African / African-American	0.0031%	32,269
European (non-Finnish)	0.00152%	65,791

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: FXN
Protein: p.Ala31=
Coding: c.93A>C
MANE Select: NM_000144
dbSNP: rs2133086878
Type: single nucleotide variant
Location: chr9:69035875 (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

Similar variants

FXN p.Leu106Ser Pathogenic ★★ same type
FXN p.Met1Ile Pathogenic ★★ same type
FXN p.Arg43His Uncertain significance ★★ ⚠ same type
FXN p.Gly138Arg Uncertain significance ★★ ⚠ same type
FXN p.Leu24Phe Uncertain significance ★★ ⚠ same type
FXN p.Leu33Val Uncertain significance ★★ ⚠ same type
FXN p.Pro30Thr Uncertain significance ★★ ⚠ same type
FXN p.Ser158Phe 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/fxn-p-ala31 (accessed [today's date]).

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