Is THUMPD1 p.Ser166fs (c.495dup) pathogenic?

THUMPD1 p.Ser166fs (c.495dup) is classified Pathogenic in THUMPD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-12-15). No gnomAD frequency available for this variant; Associated with neurodevelopmental disorder.

What condition is associated with THUMPD1 p.Ser166fs (c.495dup)?

THUMPD1 p.Ser166fs (c.495dup) is associated with neurodevelopmental disorder, neurodevelopmental disorder with speech delay and variable ocular anomalies (ClinVar).

How common is THUMPD1 p.Ser166fs (c.495dup) in the general population?

THUMPD1 p.Ser166fs (c.495dup) is no gnomAD frequency available for this variant (gnomAD).

THUMPD1 p.Ser166fs

c.495dup · rs2152417882 · VCV1333095

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.2	GERP 0.78, phastCons 1

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: THUMPD1
Protein: p.Ser166fs
Coding: c.495dup
MANE Select: NM_017736
dbSNP: rs2152417882
Type: Duplication
Location: chr16:20737867 (GRCh38)

Full THUMPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurodevelopmental disorder with speech delay and variable ocular anomalies

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/thumpd1-p-ser166fs (accessed [today's date]).

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