Is UPF3B p.Ser327= (c.981C>T) pathogenic?

UPF3B p.Ser327= (c.981C>T) is classified Likely benign in UPF3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 0.00886%, eas); Associated with syndromic X-linked intellectual disability 14.

What condition is associated with UPF3B p.Ser327= (c.981C>T)?

UPF3B p.Ser327= (c.981C>T) is associated with syndromic X-linked intellectual disability 14 (ClinVar).

How common is UPF3B p.Ser327= (c.981C>T) in the general population?

UPF3B p.Ser327= (c.981C>T) is very rare (popmax 0.00886%, eas) (gnomAD).

UPF3B p.Ser327=

c.981C>T · rs747520880 · VCV3009812

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00886%, eas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.5
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00886% East Asian · 3/33,843 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.000825% 10/1,211,571 alleles · very rare exomes 10/1,097,975 · genomes 0/113,596 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00886%	11,281
South Asian	0.00351%	28,481
African / African-American	0.00173%	57,804
European (non-Finnish)	0.000447%	223,849

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.Ser327=
Coding: c.981C>T
MANE Select: NM_080632
dbSNP: rs747520880
Type: single nucleotide variant
Location: chrX:119838393 (GRCh38)
Structure: AlphaFold pLDDT 67.35 · 3 PDB
Residue 327: 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.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-ser327 (accessed [today's date]).

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