Is SLC7A7 p.Ser417= (c.1251C>T) pathogenic?

SLC7A7 p.Ser417= (c.1251C>T) is classified Likely benign in SLC7A7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Very rare (popmax 0.00167%, amr); Associated with lysinuric protein intolerance.

What condition is associated with SLC7A7 p.Ser417= (c.1251C>T)?

SLC7A7 p.Ser417= (c.1251C>T) is associated with lysinuric protein intolerance (ClinVar).

How common is SLC7A7 p.Ser417= (c.1251C>T) in the general population?

SLC7A7 p.Ser417= (c.1251C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Lysinuric protein intolerance inherited?

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

SLC7A7 p.Ser417=

c.1251C>T · rs775549397 · VCV1147240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

lysinuric protein intolerance

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.045	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.32	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.91, phastCons 1
Overall
CADD	11.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00144% 21/1,461,852 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,506
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.00144%	69,413
South Asian	0.0011%	91,080

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.Ser417=
Coding: c.1251C>T
MANE Select: NM_003982
dbSNP: rs775549397
Type: single nucleotide variant
Location: chr14:22774111 (GRCh38)
Gene constraint: LOEUF 1.007 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.89 · 6 PDB

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 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
SLC7A7 c.999-1G>T 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/slc7a7-p-ser417 (accessed [today's date]).

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