Is ATP5F1A p.Leu26Val (c.76T>G) pathogenic?

ATP5F1A p.Leu26Val (c.76T>G) is classified Uncertain significance in ATP5F1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). AlphaMissense: likely benign (0.0569); Very rare (popmax 0.00314%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATP5F1A p.Leu26Val (c.76T>G)?

ATP5F1A p.Leu26Val (c.76T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATP5F1A p.Leu26Val (c.76T>G) in the general population?

ATP5F1A p.Leu26Val (c.76T>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about ATP5F1A p.Leu26Val (c.76T>G)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

ATP5F1A p.Leu26Val

c.76T>G · rs550057616 · VCV2174285

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,241 bp · p 0.7 · regional, not allelic
Overall
CADD	16.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,888 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00236% 38/1,613,470 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,889
Admixed American	0.00167%	59,820

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.Leu26Val
Coding: c.76T>G
MANE Select: NM_004046
dbSNP: rs550057616
Type: single nucleotide variant
Location: chr18:46095116 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 88.47 · 9 PDB

Full ATP5F1A 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

ATP5F1A p.Ala8Val Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Arg171Gln Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Arg186Gln Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Arg58Cys Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Asp357Asn Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Glu97Gln Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Ile202Val Uncertain significance ★★ ⚠ same condition
ATP5F1A p.Ile249Val 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/atp5f1a-p-leu26val (accessed [today's date]).

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