Is LAT p.Ser106= (c.318T>C) pathogenic?

LAT p.Ser106= (c.318T>C) is classified Benign/Likely benign in LAT (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-04-15). Low-frequency (popmax 1.09%, mid); Associated with severe combined immunodeficiency due to LAT deficiency.

What condition is associated with LAT p.Ser106= (c.318T>C)?

LAT p.Ser106= (c.318T>C) is associated with severe combined immunodeficiency due to LAT deficiency (ClinVar).

How common is LAT p.Ser106= (c.318T>C) in the general population?

LAT p.Ser106= (c.318T>C) is low-frequency (popmax 1.09%, mid) (gnomAD).

LAT p.Ser106=

Q: How is Severe combined immunodeficiency due to LAT deficiency inherited?

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

c.318T>C · rs140327086 · VCV1168087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, mid)

Conditions

severe combined immunodeficiency due to LAT deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.1
Overall
CADD	0.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% Middle Eastern · 66/6,052 alleles

Filtering AF 0.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.803%

Overall 0.302% 4,867/1,612,038 alleles · low-frequency exomes 4,442/1,459,806 · genomes 425/152,232 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.09%	92
Admixed American	0.516%	194
Remaining individualsnot grpmax-eligible	0.375%	267
European (non-Finnish)	0.34%	294
Ashkenazi Jewishnot grpmax-eligible	0.305%	328
South Asian	0.103%	967
African / African-American	0.068%	1,470
Finnishnot grpmax-eligible	0.025%	3,996

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: LAT
Protein: p.Ser106=
Coding: c.318T>C
MANE Select: NM_001014987
dbSNP: rs140327086
Type: single nucleotide variant
Location: chr16:28986547 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 59.77
Residue 106: a modified residue (phosphoserine); the 'disordered' region

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

Disease context

severe combined immunodeficiency due to LAT deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to LAT deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

LAT p.Leu78Pro Uncertain significance ★★ ⚠ same condition
LAT p.Pro141Leu Uncertain significance ★★ ⚠ same condition
LAT c.399-9T>A Benign ★★ same condition
LAT p.Ala120= Benign ★★ same condition
LAT p.Ala18fs Pathogenic ★ same condition
LAT p.Gly90fs Pathogenic same condition
LAT p.Leu16fs Pathogenic same condition
LAT c.-41G>T Uncertain significance ★★ same type

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/lat-p-ser106 (accessed [today's date]).

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