Is SLC7A7 p.Arg288= (c.864A>G) pathogenic?

SLC7A7 p.Arg288= (c.864A>G) is classified Likely benign in SLC7A7 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-19). Very rare (popmax 0.000763%, nfe); Associated with lysinuric protein intolerance.

What condition is associated with SLC7A7 p.Arg288= (c.864A>G)?

SLC7A7 p.Arg288= (c.864A>G) is associated with lysinuric protein intolerance (ClinVar).

How common is SLC7A7 p.Arg288= (c.864A>G) in the general population?

SLC7A7 p.Arg288= (c.864A>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

How is Lysinuric protein intolerance inherited?

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

SLC7A7 p.Arg288=

c.864A>G · rs1304389598 · VCV1144904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

lysinuric protein intolerance

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.06	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.7, phastCons 0.61
Overall
CADD	9.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,180,026 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,876 alleles · very rare

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: SLC7A7
Protein: p.Arg288=
Coding: c.864A>G
MANE Select: NM_003982
dbSNP: rs1304389598
Type: single nucleotide variant
Location: chr14:22776225 (GRCh38)
Gene constraint: LOEUF 1.007 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.89 · 6 PDB
Residue 288: an α-helix

Full SLC7A7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

lysinuric protein intolerance — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lysinuric protein intolerance (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

SLC7A7 p.Arg288fs Likely pathogenic ★★ same residue
SLC7A7 p.Arg288Thr Uncertain significance ★ ⚠ same residue
SLC7A7 c.1429+1G>C Pathogenic ★★ same condition
SLC7A7 c.625+1G>A Pathogenic ★★ same condition
SLC7A7 c.625+1G>T Pathogenic/Likely pathogenic ★★ same condition
SLC7A7 c.770+1G>T Pathogenic/Likely pathogenic ★★ same condition
SLC7A7 c.894+1G>T Pathogenic/Likely pathogenic ★★ same condition
SLC7A7 c.895-2A>G 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/slc7a7-p-arg288 (accessed [today's date]).

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