Is UPF1 p.Gln830Arg (c.2489A>G) pathogenic?

UPF1 p.Gln830Arg (c.2489A>G) is classified Likely pathogenic in UPF1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with UPF1 p.Gln830Arg (c.2489A>G)?

UPF1 p.Gln830Arg (c.2489A>G) is associated with intellectual disability (ClinVar).

How common is UPF1 p.Gln830Arg (c.2489A>G) in the general population?

UPF1 p.Gln830Arg (c.2489A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UPF1 p.Gln830Arg (c.2489A>G)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

UPF1 p.Gln830Arg

c.2489A>G · rs2055786277 · VCV930204

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar
REVEL	0.939	strongly pathogenic-leaning
SaProt	LLR -14.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 6,621 bp · p 6e-36 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q841R vs ClinVar Q830R) — verify the residue.

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: UPF1
Protein: p.Gln830Arg
Coding: c.2489A>G
MANE Select: NM_002911
dbSNP: rs2055786277
Type: single nucleotide variant
Location: chr19:18862041 (GRCh38)
Gene constraint: LOEUF 0.125 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.58 · 12 PDB
Residue 841 UniProt numbering: a turn; the upf1-type sf1b helicase c-terminal domain

Full UPF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UPF1 c.1266-32T>G Benign ★★ same type
UPF1 c.1544+108G>A Benign ★★ same type
UPF1 c.2300+75T>C Benign ★★ same type
UPF1 c.232-90G>A Benign ★★ same type
UPF1 c.2457+89G>A Benign ★★ same type
UPF1 c.2458-85G>T Benign ★★ same type
UPF1 c.2601-188G>C Benign ★★ same type
UPF1 c.2601-47A>G Benign ★★ same type

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/upf1-p-gln830arg (accessed [today's date]).

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