Is THBD p.Thr343= (c.1029A>G) pathogenic?

THBD p.Thr343= (c.1029A>G) is classified Benign/Likely benign in THBD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0736%, eas); Associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly.

What condition is associated with THBD p.Thr343= (c.1029A>G)?

THBD p.Thr343= (c.1029A>G) is associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly (ClinVar).

How common is THBD p.Thr343= (c.1029A>G) in the general population?

THBD p.Thr343= (c.1029A>G) is ultra-rare (popmax 0.0736%, eas) (gnomAD).

THBD p.Thr343=

c.1029A>G · rs79349426 · VCV337887

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, eas)

Conditions

atypical hemolytic-uremic syndrome with thrombomodulin anomaly

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 -3.1	GERP -3.1
Overall
CADD	4.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0736% East Asian · 33/44,846 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0471%

Overall 0.00217% 35/1,612,274 alleles · ultra-rare exomes 34/1,460,044 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0736%	1,359
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	8.47e-05%	1,180,013

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: THBD
Protein: p.Thr343=
Coding: c.1029A>G
MANE Select: NM_000361
dbSNP: rs79349426
Type: single nucleotide variant
Location: chr20:23048476 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 343: the egf-like 3; calcium-binding domain

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

Disease context

atypical hemolytic-uremic syndrome with thrombomodulin anomaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

THBD p.Thr343Ile Uncertain significance ★ ⚠ same residue
THBD p.Ala139Ser Uncertain significance ★★ ⚠ same condition
THBD p.Ala284Gly Uncertain significance ★★ ⚠ same condition
THBD p.Ala395Val Uncertain significance ★★ ⚠ same condition
THBD p.Ala471Thr Uncertain significance ★★ ⚠ same condition
THBD p.Ala545Thr Uncertain significance ★★ ⚠ same condition
THBD p.Arg101Leu Uncertain significance ★★ ⚠ same condition
THBD p.Arg315Leu Uncertain significance ★★ ⚠ same condition

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/thbd-p-thr343 (accessed [today's date]).

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