Is UPF3B p.Val151= (c.453C>T) pathogenic?

UPF3B p.Val151= (c.453C>T) is classified Likely benign in UPF3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). Very rare (popmax 0.00881%, sas); Associated with syndromic X-linked intellectual disability 14.

What condition is associated with UPF3B p.Val151= (c.453C>T)?

UPF3B p.Val151= (c.453C>T) is associated with syndromic X-linked intellectual disability 14 (ClinVar).

How common is UPF3B p.Val151= (c.453C>T) in the general population?

UPF3B p.Val151= (c.453C>T) is very rare (popmax 0.00881%, sas) (gnomAD).

UPF3B p.Val151=

c.453C>T · VCV4750481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00881%, sas)

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 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.35	GERP -3.2, phastCons 0.52
Overall
CADD	3.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00881% South Asian · 5/56,730 alleles

Filtering AF 0.00341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.000912% 11/1,205,734 alleles · very rare exomes 9/1,093,594 · genomes 2/112,140 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00881%	11,346
Remaining individualsnot grpmax-eligible	0.00211%	47,407
European (non-Finnish)	0.000561%	178,312

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: UPF3B
Protein: p.Val151=
Coding: c.453C>T
MANE Select: NM_080632
Type: single nucleotide variant
Location: chrX:119845214 (GRCh38)
Structure: AlphaFold pLDDT 67.35 · 3 PDB
Residue 151: the 'necessary for interaction with upf2' region; a turn

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-val151 (accessed [today's date]).

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