Is THBD p.Asp359= (c.1077C>T) pathogenic?

THBD p.Asp359= (c.1077C>T) is classified Uncertain significance in THBD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). No allele count reported in gnomAD v4.1 (AN 1,613,848).

How common is THBD p.Asp359= (c.1077C>T) in the general population?

THBD p.Asp359= (c.1077C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,848) (gnomAD).

THBD p.Asp359=

c.1077C>T · VCV4766203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,848)

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 -0.53	GERP -2.8, phastCons 0.002
Overall
CADD	7.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,848). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: THBD
Protein: p.Asp359=
Coding: c.1077C>T
MANE Select: NM_000361
Type: single nucleotide variant
Location: chr20:23048428 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 359: the egf-like 3; calcium-binding domain

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

Similar variants

THBD p.Asp359Gly Uncertain significance ★★ ⚠ same residue
THBD p.Asp359Asn Uncertain significance ★ ⚠ same residue
THBD p.Cys537Ter Pathogenic/Likely pathogenic ★★ same type
THBD p.Ala139Ser Uncertain significance ★★ ⚠ same type
THBD p.Ala21Ser Uncertain significance ★★ ⚠ same type
THBD p.Ala255Pro Uncertain significance ★★ ⚠ same type
THBD p.Ala271Thr Uncertain significance ★★ ⚠ same type
THBD p.Ala272Val 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/thbd-p-asp359 (accessed [today's date]).

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