Is UPF3B p.Val53= (c.159G>T) pathogenic?

UPF3B p.Val53= (c.159G>T) is classified Likely benign in UPF3B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability 14.

What condition is associated with UPF3B p.Val53= (c.159G>T)?

UPF3B p.Val53= (c.159G>T) is associated with syndromic X-linked intellectual disability 14 (ClinVar).

How common is UPF3B p.Val53= (c.159G>T) in the general population?

UPF3B p.Val53= (c.159G>T) is absent from gnomAD v4.1 (gnomAD).

UPF3B p.Val53=

c.159G>T · rs2521577232 · VCV2092838

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

syndromic X-linked intellectual disability 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4	GERP -0.34, phastCons 1
Overall
CADD	14.92	PHRED · no single calibrated threshold — expert panels disagree

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: UPF3B
Protein: p.Val53=
Coding: c.159G>T
MANE Select: NM_080632
dbSNP: rs2521577232
Type: single nucleotide variant
Location: chrX:119851871 (GRCh38)
Structure: AlphaFold pLDDT 67.35 · 3 PDB
Residue 53: the 'necessary for interaction with upf2' region; the 'binds to upf2' region; a β-strand

Full UPF3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

syndromic X-linked intellectual disability 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UPF3B p.Arg13Ter Likely pathogenic ★★ same condition
UPF3B p.Arg354Ter Likely pathogenic ★★ same condition
UPF3B p.Arg229Lys Uncertain significance ★★ ⚠ same condition
UPF3B p.Arg255Gly Uncertain significance ★★ same condition
UPF3B p.Arg259Lys Uncertain significance ★★ ⚠ same condition
UPF3B p.Arg313Gly Uncertain significance ★★ ⚠ same condition
UPF3B p.Arg350Gln Uncertain significance ★★ ⚠ same condition
UPF3B p.Arg368Trp 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/upf3b-p-val53 (accessed [today's date]).

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