Is PUM1 p.Trp14Ter (c.42G>A) pathogenic?

PUM1 p.Trp14Ter (c.42G>A) is classified Likely pathogenic in PUM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-05). Absent from gnomAD v4.1; Associated with PUM1-related disorder.

What condition is associated with PUM1 p.Trp14Ter (c.42G>A)?

PUM1 p.Trp14Ter (c.42G>A) is associated with PUM1-related disorder (ClinVar).

How common is PUM1 p.Trp14Ter (c.42G>A) in the general population?

PUM1 p.Trp14Ter (c.42G>A) is absent from gnomAD v4.1 (gnomAD).

PUM1 p.Trp14Ter

c.42G>A · VCV4965343

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

PUM1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 22
REVEL	0.601	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PUM1
Protein: p.Trp14Ter
Coding: c.42G>A
MANE Select: NM_001020658
Type: single nucleotide variant
Location: chr1:31059525 (GRCh38)
Gene constraint: LOEUF 0.165 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.09 · 15 PDB

Full PUM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PUM1-related disorder

Similar variants

PUM1 p.Ala571Val Uncertain significance ★★ ⚠ same condition
PUM1 p.Arg840Gln Uncertain significance ★★ ⚠ same condition
PUM1 p.Gly100Val Uncertain significance ★★ ⚠ same condition
PUM1 p.Gln626Ter Likely pathogenic ★ same condition
PUM1 p.Asp1101Asn Uncertain significance ★ ⚠ same condition
PUM1 p.Thr1035Ser Conflicting classifications of pathogenicity ★ same condition
PUM1 p.Tyr900Ter Uncertain significance ★ same condition
PUM1 p.Pro622Ser 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/pum1-p-trp14ter (accessed [today's date]).

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