Is SLC5A1 p.Pro552= (c.1656G>A) pathogenic?

SLC5A1 p.Pro552= (c.1656G>A) is classified Likely benign in SLC5A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-19). Very rare (popmax 0.00679%, nfe); Associated with glucose-galactose malabsorption.

What condition is associated with SLC5A1 p.Pro552= (c.1656G>A)?

SLC5A1 p.Pro552= (c.1656G>A) is associated with glucose-galactose malabsorption (ClinVar).

How common is SLC5A1 p.Pro552= (c.1656G>A) in the general population?

SLC5A1 p.Pro552= (c.1656G>A) is very rare (popmax 0.00679%, nfe) (gnomAD).

How is Glucose-galactose malabsorption inherited?

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

SLC5A1 p.Pro552=

c.1656G>A · rs375169164 · VCV2052077

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00679%, nfe)

Conditions

glucose-galactose malabsorption

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -3.7
Overall
CADD	6.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00679% European (non-Finnish) · 80/1,177,560 alleles

Filtering AF 0.00556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00633% 102/1,611,128 alleles · very rare exomes 93/1,459,142 · genomes 9/151,986 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00801%	12,477
European (non-Finnish)grpmax	0.00679%	14,719
South Asian	0.00659%	15,173
African / African-American	0.00535%	18,695
Finnishnot grpmax-eligible	0.00469%	21,333
East Asian	0.00446%	22,433
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,586
Admixed American	0.00167%	59,974

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro552=
Coding: c.1656G>A
MANE Select: NM_000343
dbSNP: rs375169164
Type: single nucleotide variant
Location: chr22:32102228 (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 552: an α-helix; a UniProt-annotated variant site (in ggm; loss of activity); a UniProt-annotated variant site (in ggm)

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

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SLC5A1 p.Cys255Trp Pathogenic ★★ same condition
SLC5A1 p.Gln457Arg Pathogenic/Likely pathogenic ★★ same condition
SLC5A1 p.Ser159Pro Likely pathogenic ★★ same condition
SLC5A1 p.Trp67Ter 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-pro552 (accessed [today's date]).

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