Is SLC25A11 p.Leu26Val (c.76C>G) pathogenic?

SLC25A11 p.Leu26Val (c.76C>G) is classified Uncertain significance in SLC25A11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely benign (0.1054); Ultra-rare (popmax 0.01%, amr).

How common is SLC25A11 p.Leu26Val (c.76C>G) in the general population?

SLC25A11 p.Leu26Val (c.76C>G) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about SLC25A11 p.Leu26Val (c.76C>G)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

SLC25A11 p.Leu26Val

c.76C>G · VCV4706896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 0.76, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 963 bp · p 0.11 · regional, not allelic
Overall
CADD	22.5	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 0.01% Admixed American · 6/59,962 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00155% 25/1,612,670 alleles · ultra-rare exomes 23/1,460,382 · genomes 2/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,994
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.00153%	65,536

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: SLC25A11
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_003562
Type: single nucleotide variant
Location: chr17:4939835 (GRCh38)
Gene constraint: LOEUF 0.527 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 87.54

Full SLC25A11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC25A11 p.Arg158Gly Uncertain significance ★★ ⚠ same type
SLC25A11 p.Arg309Cys Uncertain significance ★★ ⚠ same type
SLC25A11 p.Leu109= Likely benign ★★ same type
SLC25A11 p.Leu88= Benign/Likely benign ★★ same type
SLC25A11 p.Val164= Likely benign ★★ same type
SLC25A11 p.Ala191Thr Uncertain significance ★ ⚠ same type
SLC25A11 p.Ala243Thr Uncertain significance ★ ⚠ same type
SLC25A11 p.Ala306Val 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/slc25a11-p-leu26val (accessed [today's date]).

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