ATP5F1A p.Phe449=
c.1347C>T · rs141613719 · VCV2164592
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0203%, 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 -3.3 | GERP -4.3 |
| Overall | ||
| CADD | 7.568 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0203%
Middle Eastern · 1/4,932 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00577%
93/1,612,600 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0203% | 4,932 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,907 |
| European (non-Finnish) | 0.00636% | 15,734 |
| South Asian | 0.00439% | 22,755 |
| African / African-American | 0.00401% | 24,945 |
| Admixed American | 0.00333% | 29,998 |
| East Asian | 0.00223% | 44,888 |
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
- ATP5F1A
- Protein
- p.Phe449=
- Coding
- c.1347C>T
- MANE Select
- NM_004046
- dbSNP
- rs141613719
- Type
- single nucleotide variant
- Location
- chr18:46086195 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI 0.29 (gnomAD)
- Structure
- AlphaFold pLDDT 88.47 · 9 PDB
- Residue 449
- a turn
Similar variants
- ATP5F1A c.1176+1G>C Likely pathogenic ★★ same type
- ATP5F1A p.Arg182Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- ATP5F1A p.Arg207His Pathogenic/Likely pathogenic ★★ same type
- ATP5F1A p.Gly418Arg Likely pathogenic ★★ same type
- ATP5F1A p.Ala49Val Uncertain significance ★★ ⚠ same type
- ATP5F1A p.Ala8Val Uncertain significance ★★ ⚠ same type
- ATP5F1A p.Arg169Cys Uncertain significance ★★ ⚠ same type
- ATP5F1A p.Arg171Gln 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/atp5f1a-p-phe449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown