Is AIFM1 p.Pro554= (c.1662C>T) pathogenic?

AIFM1 p.Pro554= (c.1662C>T) is classified Likely benign in AIFM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-07). Very rare (popmax 0.00346%, afr); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with AIFM1 p.Pro554= (c.1662C>T)?

AIFM1 p.Pro554= (c.1662C>T) is associated with Charcot-Marie-Tooth Neuropathy X, combined oxidative phosphorylation deficiency (ClinVar).

How common is AIFM1 p.Pro554= (c.1662C>T) in the general population?

AIFM1 p.Pro554= (c.1662C>T) is very rare (popmax 0.00346%, afr) (gnomAD).

AIFM1 p.Pro554=

c.1662C>T · rs2029999691 · VCV1580536

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00346%, 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 -3.1	GERP -3.2
Overall
CADD	0.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00346% African / African-American · 2/57,826 alleles

Filtering AF 0.000574% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.00082% 9/1,098,111 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00346%	28,913
South Asian	0.00175%	56,990
European (non-Finnish)	0.00067%	149,242

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.Pro554=
Coding: c.1662C>T
MANE Select: NM_004208
dbSNP: rs2029999691
Type: single nucleotide variant
Location: chrX:130130078 (GRCh38)
Structure: AlphaFold pLDDT 85.97 · 26 PDB
Residue 554: the 'disordered' region

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.Pro554Ser Uncertain significance ★ ⚠ 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-pro554 (accessed [today's date]).

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