Is SLC5A2 p.Val425= (c.1275G>A) pathogenic?

SLC5A2 p.Val425= (c.1275G>A) is classified Conflicting classifications of pathogenicity in SLC5A2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-04-02). Ultra-rare (popmax 0.0712%, nfe); Associated with familial renal glucosuria.

What condition is associated with SLC5A2 p.Val425= (c.1275G>A)?

SLC5A2 p.Val425= (c.1275G>A) is associated with familial renal glucosuria (ClinVar).

How common is SLC5A2 p.Val425= (c.1275G>A) in the general population?

SLC5A2 p.Val425= (c.1275G>A) is ultra-rare (popmax 0.0712%, nfe) (gnomAD).

How is Familial renal glucosuria inherited?

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

SLC5A2 p.Val425=

c.1275G>A · rs183103554 · VCV884766

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0712%, nfe)

Conditions

familial renal glucosuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.68	donor gain · deltas
Pangolin	Δ0.69	gain · loss 0.14 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.8	GERP -3.7
Overall
CADD	15.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0712% European (non-Finnish) · 838/1,177,408 alleles

Filtering AF 0.0672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0656%

Overall 0.0562% 900/1,601,842 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0712%	1,405
Ashkenazi Jewishnot grpmax-eligible	0.0578%	1,730
Remaining individualsnot grpmax-eligible	0.0371%	2,699
Admixed American	0.0202%	4,951
African / African-American	0.0107%	9,367
East Asian	0.00224%	44,586
Finnishnot grpmax-eligible	0.00177%	56,484

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: SLC5A2
Protein: p.Val425=
Coding: c.1275G>A
MANE Select: NM_003041
dbSNP: rs183103554
Type: single nucleotide variant
Location: chr16:31488767 (GRCh38)
Gene constraint: LOEUF 1.21 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.32 · 12 PDB
Residue 425: a disulfide bond; an α-helix

Full SLC5A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial renal glucosuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial renal glucosuria (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

SLC5A2 p.Val425Glu Uncertain significance ★ ⚠ same residue
SLC5A2 c.1280+1G>A Likely pathogenic ★★ same condition
SLC5A2 p.Arg368Trp Likely pathogenic ★★ ⚠ same condition
SLC5A2 p.Lys321Arg Pathogenic/Likely pathogenic ★★ same condition
SLC5A2 c.469-3A>T Uncertain significance ★★ same condition
SLC5A2 p.Ala102Val Uncertain significance ★★ ⚠ same condition
SLC5A2 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
SLC5A2 p.Ala549Val 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/slc5a2-p-val425 (accessed [today's date]).

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