Is SLC5A2 p.Pro514Ser (c.1540C>T) pathogenic?

SLC5A2 p.Pro514Ser (c.1540C>T) is classified Likely pathogenic in SLC5A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely benign (0.1298); Rare (popmax 0.123%, eas); Associated with familial renal glucosuria.

What condition is associated with SLC5A2 p.Pro514Ser (c.1540C>T)?

SLC5A2 p.Pro514Ser (c.1540C>T) is associated with familial renal glucosuria (ClinVar).

How common is SLC5A2 p.Pro514Ser (c.1540C>T) in the general population?

SLC5A2 p.Pro514Ser (c.1540C>T) is rare (popmax 0.123%, eas) (gnomAD).

How is Familial renal glucosuria inherited?

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

What do computational predictors say about SLC5A2 p.Pro514Ser (c.1540C>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

SLC5A2 p.Pro514Ser

c.1540C>T · VCV3580355

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial renal glucosuria

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign ⚠ discordant with ClinVar
REVEL	0.603	indeterminate
SaProt	LLR -9.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 7,395 bp · p 0.0088 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% East Asian · 55/44,880 alleles

Filtering AF 0.0967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0873%

Overall 0.00366% 59/1,610,226 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.123%	816
Remaining individualsnot grpmax-eligible	0.0064%	15,619

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.Pro514Ser
Coding: c.1540C>T
MANE Select: NM_003041
Type: single nucleotide variant
Location: chr16:31489213 (GRCh38)
Gene constraint: LOEUF 1.21 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.32 · 12 PDB

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 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
SLC5A2 p.Arg130His 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-pro514ser (accessed [today's date]).

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