Is THBD p.Asn299= (c.897C>T) pathogenic?

THBD p.Asn299= (c.897C>T) is classified Conflicting classifications of pathogenicity in THBD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-11). Very rare (popmax 0.000933%, nfe); Associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly.

What condition is associated with THBD p.Asn299= (c.897C>T)?

THBD p.Asn299= (c.897C>T) is associated with atypical hemolytic-uremic syndrome with thrombomodulin anomaly (ClinVar).

How common is THBD p.Asn299= (c.897C>T) in the general population?

THBD p.Asn299= (c.897C>T) is very rare (popmax 0.000933%, nfe) (gnomAD).

THBD p.Asn299=

c.897C>T · rs1008621697 · VCV896685

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

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 0.86	GERP -0.51
Overall
CADD	7.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,530 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000688% 11/1,598,414 alleles · very rare exomes 8/1,446,146 · genomes 3/152,268 · 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: THBD
Protein: p.Asn299=
Coding: c.897C>T
MANE Select: NM_000361
dbSNP: rs1008621697
Type: single nucleotide variant
Location: chr20:23048608 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 299: the egf-like 2 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.Asn299Thr Uncertain significance ★ ⚠ same residue
THBD p.Asn299Ile Uncertain significance ★★ ⚠ same residue
THBD p.Asn299Lys Uncertain significance ★ ⚠ same residue
THBD p.Asn299Ser 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

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-asn299 (accessed [today's date]).

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