Is LAT p.Ile49Phe (c.145A>T) pathogenic?

LAT p.Ile49Phe (c.145A>T) is classified Uncertain significance in LAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). AlphaMissense: likely benign (0.1553); Very rare (popmax 0.000763%, nfe).

How common is LAT p.Ile49Phe (c.145A>T) in the general population?

LAT p.Ile49Phe (c.145A>T) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about LAT p.Ile49Phe (c.145A>T)?

AlphaMissense predicts likely benign (score 0.1553) — an in-silico prediction, not a clinical call.

LAT p.Ile49Phe

c.145A>T · rs141916698 · VCV1525329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1553 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1553	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.2	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 4,591 bp · p 0.0017 · regional, not allelic
Overall
CADD	17.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,986 alleles

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

Overall 0.000558% 9/1,613,972 alleles · very rare exomes 7/1,461,848 · genomes 2/152,124 · joint denominator

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.Ile49Phe
Coding: c.145A>T
MANE Select: NM_001014987
dbSNP: rs141916698
Type: single nucleotide variant
Location: chr16:28985870 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 59.77

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

Similar variants

LAT c.-41G>T Uncertain significance ★★ same type
LAT p.Ala183Val Uncertain significance ★★ ⚠ same type
LAT p.Arg53Gln Uncertain significance ★★ ⚠ same type
LAT p.Arg93Gln Uncertain significance ★★ ⚠ same type
LAT p.Arg93Trp Uncertain significance ★★ ⚠ same type
LAT p.Arg98Gln Uncertain significance ★★ ⚠ same type
LAT p.Arg98Trp Uncertain significance ★★ ⚠ same type
LAT p.Asp126Val 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-ile49phe (accessed [today's date]).

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