Is SLC5A6 p.Val504Leu (c.1510G>C) pathogenic?

SLC5A6 p.Val504Leu (c.1510G>C) is classified Uncertain significance in SLC5A6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.0951); Very rare (popmax 0.00822%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SLC5A6 p.Val504Leu (c.1510G>C)?

SLC5A6 p.Val504Leu (c.1510G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SLC5A6 p.Val504Leu (c.1510G>C) in the general population?

SLC5A6 p.Val504Leu (c.1510G>C) is very rare (popmax 0.00822%, nfe) (gnomAD).

What do computational predictors say about SLC5A6 p.Val504Leu (c.1510G>C)?

AlphaMissense predicts likely benign (score 0.0951) — an in-silico prediction, not a clinical call.

SLC5A6 p.Val504Leu

c.1510G>C · VCV3798126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00822%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0951	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.06	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 -1.7	GERP -4.7
Regional constraint	o/e 0.83	unconstrained · MANE · 7,211 bp · p 9.5e-07 · regional, not allelic
Overall
CADD	0.31	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 0.00822% European (non-Finnish) · 97/1,180,010 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00638% 103/1,614,076 alleles · very rare exomes 98/1,461,844 · genomes 5/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00822%	12,165
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00133%	74,948

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: SLC5A6
Protein: p.Val504Leu
Coding: c.1510G>C
MANE Select: NM_021095
Type: single nucleotide variant
Location: chr2:27201700 (GRCh38)
Gene constraint: LOEUF 0.609 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 79.99 · 5 PDB
Residue 504: a UniProt-annotated variant site (in smvtd and comnb; reduced membrane localization; impaired biotin transport)

Full SLC5A6 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

SLC5A6 p.Arg285Cys Uncertain significance ★★ ⚠ same condition
SLC5A6 p.Arg53Gln Uncertain significance ★★ ⚠ same condition
SLC5A6 p.Val189Ile Likely benign ★★ same condition
SLC5A6 p.Ala192Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala317Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala357Val Uncertain significance ★ ⚠ same condition
SLC5A6 p.Ala41Gly Uncertain significance ★ ⚠ same condition
SLC5A6 p.Arg240Cys 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/slc5a6-p-val504leu (accessed [today's date]).

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