Is LTA p.Cys13Arg (c.37T>C) pathogenic?

LTA p.Cys13Arg (c.37T>C) is classified Benign in LTA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). AlphaMissense: likely benign (0.0443); Common (popmax 33.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with LTA-related disorder.

What condition is associated with LTA p.Cys13Arg (c.37T>C)?

LTA p.Cys13Arg (c.37T>C) is associated with LTA-related disorder (ClinVar).

What do computational predictors say about LTA p.Cys13Arg (c.37T>C)?

AlphaMissense predicts likely benign (score 0.0443) — an in-silico prediction, not a clinical call.

LTA p.Cys13Arg

Q: How common is LTA p.Cys13Arg (c.37T>C) in the general population?

LTA p.Cys13Arg (c.37T>C) is common (popmax 33.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.37T>C · rs2229094 · VCV3059641

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0443 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 33.4%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

LTA-related disorder

Computational evidence

Protein change
AlphaMissense	0.0443	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.028	GERP -2.4, phastCons 0.005
Overall
CADD	7.259	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.4% South Asian · 30,401/91,006 alleles

Filtering AF 33.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 33%

Overall 26.3% 423,286/1,609,528 alleles · common exomes 382,238/1,458,298 · genomes 41,048/151,230 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	33.4%	3
Finnishnot grpmax-eligible	33.1%	3
Amishnot grpmax-eligible	30.7%	3
Ashkenazi Jewishnot grpmax-eligible	29.9%	3
Middle Eastern	29.5%	3
African / African-American	27.9%	4
Remaining individualsnot grpmax-eligible	27.2%	4
European (non-Finnish)	25.6%	4
Admixed American	22.1%	5
East Asian	18.5%	5

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.Cys13Arg
Coding: c.37T>C
MANE Select: NM_000595
dbSNP: rs2229094
Type: single nucleotide variant
Location: chr6:31572779 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 83.96 · 3 PDB
Residue 13: a UniProt-annotated variant site (in)

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

Disease context

LTA-related disorder

Similar variants

LTA p.Ala64= Likely 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-cys13arg (accessed [today's date]).

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