Is LTA p.Ala64= (c.192T>C) pathogenic?

LTA p.Ala64= (c.192T>C) is classified Likely benign in LTA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-12). Very rare (popmax 0.000339%, nfe); Associated with LTA-related disorder.

What condition is associated with LTA p.Ala64= (c.192T>C)?

LTA p.Ala64= (c.192T>C) is associated with LTA-related disorder (ClinVar).

How common is LTA p.Ala64= (c.192T>C) in the general population?

LTA p.Ala64= (c.192T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

LTA p.Ala64=

c.192T>C · rs1196374898 · VCV3050752

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

LTA-related disorder

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 -8.9	GERP -3.1
Overall
CADD	1.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,678 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,234 alleles · very rare exomes 3/1,460,396 · genomes 1/151,838 · 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: LTA
Protein: p.Ala64=
Coding: c.192T>C
MANE Select: NM_000595
dbSNP: rs1196374898
Type: single nucleotide variant
Location: chr6:31573020 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 83.96 · 3 PDB
Residue 64: a β-strand; the thd domain

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

Disease context

LTA-related disorder

Similar variants

LTA p.Cys13Arg Benign same condition
LTA p.Ala171Thr Uncertain significance ★ ⚠ same type
LTA p.Gln141Pro Uncertain significance ★ ⚠ same type
LTA p.Gly91Arg Uncertain significance ★ ⚠ same type
LTA p.His51Asn Uncertain significance ★ ⚠ same type
LTA p.Ile106Val Uncertain significance ★ ⚠ same type
LTA p.Leu35Ile Uncertain significance ★ ⚠ same type
LTA p.Lys53Arg 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/lta-p-ala64 (accessed [today's date]).

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