Is LAT p.Ala63= (c.189C>G) pathogenic?

LAT p.Ala63= (c.189C>G) is classified Likely benign in LAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-21). Very rare (popmax 0.00034%, nfe).

How common is LAT p.Ala63= (c.189C>G) in the general population?

LAT p.Ala63= (c.189C>G) is very rare (popmax 0.00034%, nfe) (gnomAD).

LAT p.Ala63=

c.189C>G · VCV3698543

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1
Overall
CADD	2.755	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,174,852 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000249% 4/1,603,568 alleles · very rare exomes 3/1,451,470 · genomes 1/152,098 · 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.Ala63=
Coding: c.189C>G
MANE Select: NM_001014987
Type: single nucleotide variant
Location: chr16:28986160 (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-ala63 (accessed [today's date]).

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