Is THBD p.Glu361= (c.1083G>A) pathogenic?

THBD p.Glu361= (c.1083G>A) is classified Likely benign in THBD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-31). Ultra-rare (popmax 0.029%, eas); Associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly.

How common is THBD p.Glu361= (c.1083G>A) in the general population?

THBD p.Glu361= (c.1083G>A) is ultra-rare (popmax 0.029%, eas) (gnomAD).

THBD p.Glu361=

Q: What condition is associated with THBD p.Glu361= (c.1083G>A)?

THBD p.Glu361= (c.1083G>A) is associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly, atypical hemolytic-uremic syndrome (ClinVar).

c.1083G>A · rs370377519 · VCV337886

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, 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 0.39	GERP -0.72, phastCons 0.99
Overall
CADD	10.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,886 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00192% 31/1,613,856 alleles · ultra-rare exomes 27/1,461,634 · genomes 4/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,453
Remaining individualsnot grpmax-eligible	0.0288%	3,472

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.Glu361=
Coding: c.1083G>A
MANE Select: NM_000361
dbSNP: rs370377519
Type: single nucleotide variant
Location: chr20:23048422 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 361: 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

Also linked: atypical hemolytic-uremic syndrome

Similar variants

THBD p.Glu361Asp Uncertain significance ★ ⚠ same residue
THBD p.Glu361Lys Uncertain significance ★ ⚠ same residue
THBD p.Ala139Ser Uncertain significance ★★ ⚠ same condition
THBD p.Ala255Pro 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

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-glu361 (accessed [today's date]).

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