Is SLC7A7 p.Phe152= (c.456C>T) pathogenic?

SLC7A7 p.Phe152= (c.456C>T) is classified Benign in SLC7A7 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Common (popmax 9.69%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autoinflammatory syndrome.

What condition is associated with SLC7A7 p.Phe152= (c.456C>T)?

SLC7A7 p.Phe152= (c.456C>T) is associated with autoinflammatory syndrome, lysinuric protein intolerance (ClinVar).

SLC7A7 p.Phe152=

Q: How common is SLC7A7 p.Phe152= (c.456C>T) in the general population?

SLC7A7 p.Phe152= (c.456C>T) is common (popmax 9.69%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.456C>T · rs8016634 · VCV312824

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 9.69%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autoinflammatory syndrome

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 -4.7	GERP -4.7
Overall
CADD	7.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.69% African / African-American · 7,260/74,898 alleles

Filtering AF 9.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.43%

Overall 0.629% 10,152/1,613,798 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.69%	10
Middle Eastern	1.2%	83
Remaining individualsnot grpmax-eligible	0.842%	119
Admixed American	0.807%	124
Ashkenazi Jewishnot grpmax-eligible	0.355%	282
South Asian	0.314%	318
European (non-Finnish)	0.12%	835
Finnishnot grpmax-eligible	0.00469%	21,301
East Asian	0.00223%	44,878

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.Phe152=
Coding: c.456C>T
MANE Select: NM_003982
dbSNP: rs8016634
Type: single nucleotide variant
Location: chr14:22812943 (GRCh38)
Gene constraint: LOEUF 1.007 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.89 · 6 PDB
Residue 152: a UniProt-annotated variant site (in lpi; moderately reduced cationic amino acid transport activity); an α-helix

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lysinuric protein intolerance

Similar variants

SLC7A7 p.Phe152Leu 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
SLC7A7 c.895-2A>T 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-phe152 (accessed [today's date]).

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