Is THBD p.Cys175fs (c.523_533del) pathogenic?

THBD p.Cys175fs (c.523533del) is classified Uncertain significance in THBD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). No gnomAD frequency available for this variant.

How common is THBD p.Cys175fs (c.523_533del) in the general population?

THBD p.Cys175fs (c.523_533del) is no gnomAD frequency available for this variant (gnomAD).

THBD p.Cys175fs

c.523_533del · rs2515205255 · VCV2692813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.24	GERP 0.65, phastCons 0.01

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Cys175fs
Coding: c.523_533del
MANE Select: NM_000361
dbSNP: rs2515205255
Type: Deletion
Location: chr20:23048972 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB

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

Similar variants

THBD p.Cys175Ser Uncertain significance ★★ ⚠ same residue
THBD p.Pro496fs Likely pathogenic ★★ same type
THBD p.Glu144_Thr146del Uncertain significance ★★ same type
THBD p.Ala43fs Likely pathogenic ★ same type
THBD p.Cys349fs Likely pathogenic ★ same type
THBD p.Val454fs Likely pathogenic ★ same type
THBD p.Arg264fs Uncertain significance ★ same type
THBD p.Asp418fs 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-cys175fs (accessed [today's date]).

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