Is SLC5A1 p.Pro69= (c.207G>A) pathogenic?

SLC5A1 p.Pro69= (c.207G>A) is classified Uncertain significance in SLC5A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Ultra-rare (popmax 0.0111%, eas); Associated with glucose-galactose malabsorption.

What condition is associated with SLC5A1 p.Pro69= (c.207G>A)?

SLC5A1 p.Pro69= (c.207G>A) is associated with glucose-galactose malabsorption (ClinVar).

How common is SLC5A1 p.Pro69= (c.207G>A) in the general population?

SLC5A1 p.Pro69= (c.207G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Glucose-galactose malabsorption inherited?

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

SLC5A1 p.Pro69=

c.207G>A · VCV3587885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

glucose-galactose malabsorption

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.52	donor loss · deltas
Constraint at this position
Conservation	phyloP 6.3	GERP 1.7, phastCons 1
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,868 alleles

Filtering AF 0.00487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00539% 87/1,612,856 alleles · ultra-rare exomes 81/1,460,616 · genomes 6/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,974
European (non-Finnish)	0.00602%	16,604
South Asian	0.00439%	22,769
African / African-American	0.004%	24,997
Remaining individualsnot grpmax-eligible	0.0032%	31,234
Finnishnot grpmax-eligible	0.00312%	32,007

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: SLC5A1
Protein: p.Pro69=
Coding: c.207G>A
MANE Select: NM_000343
Type: single nucleotide variant
Location: chr22:32050014 (GRCh38)
Gene constraint: LOEUF 0.705 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.53 · 4 PDB
Residue 69: an α-helix

Full SLC5A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glucose-galactose malabsorption — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glucose-galactose malabsorption (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SLC5A1 p.Pro69Leu Uncertain significance ★ ⚠ same residue
SLC5A1 p.Arg267Ter Pathogenic ★★ same condition
SLC5A1 p.Arg336His Likely pathogenic ★★ same condition
SLC5A1 p.Arg63Ter Pathogenic ★★ same condition
SLC5A1 p.Asp28Asn Pathogenic/Likely pathogenic ★★ same condition
SLC5A1 p.Cys255Trp Pathogenic ★★ same condition
SLC5A1 p.Gln457Arg Pathogenic/Likely pathogenic ★★ same condition
SLC5A1 p.Ser159Pro Likely pathogenic ★★ 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/slc5a1-p-pro69 (accessed [today's date]).

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