Is AIFM1 p.Pro488= (c.1464C>T) pathogenic?

AIFM1 p.Pro488= (c.1464C>T) is classified Likely benign in AIFM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-07). Ultra-rare (popmax 0.0122%, afr); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with AIFM1 p.Pro488= (c.1464C>T)?

AIFM1 p.Pro488= (c.1464C>T) is associated with Charcot-Marie-Tooth Neuropathy X, combined oxidative phosphorylation deficiency (ClinVar).

How common is AIFM1 p.Pro488= (c.1464C>T) in the general population?

AIFM1 p.Pro488= (c.1464C>T) is ultra-rare (popmax 0.0122%, afr) (gnomAD).

AIFM1 p.Pro488=

c.1464C>T · rs146608893 · VCV774027

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, afr)

Conditions

Charcot-Marie-Tooth Neuropathy X

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 -4.6	GERP -3.5
Overall
CADD	0.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0122% African / African-American · 7/57,303 alleles

Filtering AF 0.00566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00405%

Overall 0.000909% 11/1,210,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0122%	8,186
Finnishnot grpmax-eligible	0.00214%	46,629
Remaining individualsnot grpmax-eligible	0.0021%	47,597
European (non-Finnish)	0.000223%	447,547

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: AIFM1
Protein: p.Pro488=
Coding: c.1464C>T
MANE Select: NM_004208
dbSNP: rs146608893
Type: single nucleotide variant
Location: chrX:130131784 (GRCh38)
Structure: AlphaFold pLDDT 85.97 · 26 PDB

Full AIFM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth Neuropathy X — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined oxidative phosphorylation deficiency

Similar variants

AIFM1 p.Pro488Leu Pathogenic ⚠ same residue
AIFM1 p.Arg422Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
AIFM1 p.Arg422Trp Pathogenic/Likely pathogenic ★★ same condition
AIFM1 p.Met340Thr Pathogenic/Likely pathogenic ★★ same condition
AIFM1 c.1448+5T>C Uncertain significance ★★ same condition
AIFM1 c.782-3C>T Uncertain significance ★★ same condition
AIFM1 p.Ala117Val Uncertain significance ★★ ⚠ same condition
AIFM1 p.Ala80Thr 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/aifm1-p-pro488 (accessed [today's date]).

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