Is FXN p.Asp178= (c.534C>T) pathogenic?

FXN p.Asp178= (c.534C>T) is classified Benign/Likely benign in FXN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). Ultra-rare (popmax 0.03%, amr); Associated with Inborn genetic diseases.

What condition is associated with FXN p.Asp178= (c.534C>T)?

FXN p.Asp178= (c.534C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FXN p.Asp178= (c.534C>T) in the general population?

FXN p.Asp178= (c.534C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

FXN p.Asp178=

c.534C>T · rs61754561 · VCV264460

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.461	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -13	GERP -4.3
Overall
CADD	7.693	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,004 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0203%

Overall 0.02% 323/1,614,028 alleles · ultra-rare exomes 284/1,461,892 · genomes 39/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,334
European (non-Finnish)	0.0235%	4,260
Finnishnot grpmax-eligible	0.0141%	7,115
African / African-American	0.012%	8,320
Remaining individualsnot grpmax-eligible	0.0096%	10,415
South Asian	0.00329%	30,361
East Asian	0.00223%	44,892

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.Asp178=
Coding: c.534C>T
MANE Select: NM_000144
dbSNP: rs61754561
Type: single nucleotide variant
Location: chr9:69072663 (GRCh38)
Gene constraint: LOEUF 0.809 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 75.93 · 19 PDB
Residue 178: a turn

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.Asp209Gly Benign/Likely benign ★★ same condition
FXN p.Leu156= 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-asp178 (accessed [today's date]).

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