Is SLC30A10 p.Leu26Val (c.76C>G) pathogenic?

SLC30A10 p.Leu26Val (c.76C>G) is classified Uncertain significance in SLC30A10 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1642); Very rare (popmax 0.00134%, afr); Associated with cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome.

What condition is associated with SLC30A10 p.Leu26Val (c.76C>G)?

SLC30A10 p.Leu26Val (c.76C>G) is associated with cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (ClinVar).

How common is SLC30A10 p.Leu26Val (c.76C>G) in the general population?

SLC30A10 p.Leu26Val (c.76C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about SLC30A10 p.Leu26Val (c.76C>G)?

AlphaMissense predicts likely benign (score 0.1642) — an in-silico prediction, not a clinical call.

SLC30A10 p.Leu26Val

Q: How is Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.76C>G · rs774149422 · VCV295594

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome

Computational evidence

Protein change
AlphaMissense	0.1642	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 0.66, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 13 kb · p 1.6e-06 · regional, not allelic
Overall
CADD	24.8	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 0.00134% African / African-American · 1/74,894 alleles

Overall 0.000124% 2/1,613,308 alleles · very rare exomes 1/1,461,158 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,894
European (non-Finnish)	8.48e-05%	1,179,711

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: SLC30A10
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_018713
dbSNP: rs774149422
Type: single nucleotide variant
Location: chr1:219928365 (GRCh38)
Gene constraint: LOEUF 0.99 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 67.63 · 3 PDB

Full SLC30A10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SLC30A10 p.Ala303Thr Uncertain significance ★★ ⚠ same condition
SLC30A10 p.Gly161Val Uncertain significance ★★ ⚠ same condition
SLC30A10 p.Gly467Arg Uncertain significance ★★ ⚠ same condition
SLC30A10 p.Met226Val Uncertain significance ★★ ⚠ same condition
SLC30A10 c.640+10G>A Benign/Likely benign ★★ same condition
SLC30A10 c.-54C>A Benign ★★ same condition
SLC30A10 c.-87A>T Likely benign ★★ same condition
SLC30A10 c.*1088G>A Benign ★★ 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/slc30a10-p-leu26val (accessed [today's date]).

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