Is SLC7A7 p.Phe430= (c.1290C>T) pathogenic?

SLC7A7 p.Phe430= (c.1290C>T) is classified Likely benign in SLC7A7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). Very rare (popmax 8.47e-05%, nfe); Associated with lysinuric protein intolerance.

What condition is associated with SLC7A7 p.Phe430= (c.1290C>T)?

SLC7A7 p.Phe430= (c.1290C>T) is associated with lysinuric protein intolerance (ClinVar).

How common is SLC7A7 p.Phe430= (c.1290C>T) in the general population?

SLC7A7 p.Phe430= (c.1290C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Lysinuric protein intolerance inherited?

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

SLC7A7 p.Phe430=

c.1290C>T · rs368164901 · VCV1582888

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

lysinuric protein intolerance

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.419	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.7	GERP 1.8, phastCons 1
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 0.000124% 2/1,614,200 alleles · very rare exomes 2/1,461,880 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	8.47e-05%	1,180,036

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: SLC7A7
Protein: p.Phe430=
Coding: c.1290C>T
MANE Select: NM_003982
dbSNP: rs368164901
Type: single nucleotide variant
Location: chr14:22774072 (GRCh38)
Gene constraint: LOEUF 1.007 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.89 · 6 PDB
Residue 430: 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.Phe430Val Uncertain significance ★ ⚠ same residue
SLC7A7 p.Phe430fs Pathogenic/Likely pathogenic ★★ 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-phe430 (accessed [today's date]).

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