Is UPF3B p.Phe386= (c.1158T>C) pathogenic?

UPF3B p.Phe386= (c.1158T>C) is classified Likely benign in UPF3B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-25). Very rare (popmax 0.000894%, nfe); Associated with syndromic X-linked intellectual disability 14.

What condition is associated with UPF3B p.Phe386= (c.1158T>C)?

UPF3B p.Phe386= (c.1158T>C) is associated with syndromic X-linked intellectual disability 14 (ClinVar).

How common is UPF3B p.Phe386= (c.1158T>C) in the general population?

UPF3B p.Phe386= (c.1158T>C) is very rare (popmax 0.000894%, nfe) (gnomAD).

UPF3B p.Phe386=

c.1158T>C · rs2056117477 · VCV1554503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000894%, nfe)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	GERP -0.45, phastCons 1
Overall
CADD	7.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000894% European (non-Finnish) · 8/895,304 alleles

Filtering AF 0.000384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000661% 8/1,210,336 alleles · very rare exomes 8/1,097,784 · genomes 0/112,552 · joint denominator

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.Phe386=
Coding: c.1158T>C
MANE Select: NM_080632
dbSNP: rs2056117477
Type: single nucleotide variant
Location: chrX:119837901 (GRCh38)
Structure: AlphaFold pLDDT 67.35 · 3 PDB
Residue 386: the 'disordered' region

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.Phe386Ser Uncertain significance ★★ ⚠ same residue
UPF3B p.Phe386Tyr Uncertain significance ★ ⚠ same residue
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

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-phe386 (accessed [today's date]).

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