Is UBAP1 p.Arg220Trp (c.658C>T) pathogenic?

UBAP1 p.Arg220Trp (c.658C>T) is classified Conflicting classifications of pathogenicity in UBAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1017); Rare (popmax 0.165%, afr); Associated with Inborn genetic diseases.

What condition is associated with UBAP1 p.Arg220Trp (c.658C>T)?

UBAP1 p.Arg220Trp (c.658C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBAP1 p.Arg220Trp (c.658C>T) in the general population?

UBAP1 p.Arg220Trp (c.658C>T) is rare (popmax 0.165%, afr) (gnomAD).

What do computational predictors say about UBAP1 p.Arg220Trp (c.658C>T)?

AlphaMissense predicts likely benign (score 0.1017) — an in-silico prediction, not a clinical call.

UBAP1 p.Arg220Trp

c.658C>T · VCV4194757

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1017 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.165%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1017	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 9,962 bp · p 0.0098 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% African / African-American · 124/74,974 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.0121% 196/1,613,968 alleles · rare exomes 129/1,461,826 · genomes 67/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.165%	605
Remaining individualsnot grpmax-eligible	0.0176%	5,682
South Asian	0.00659%	15,180
Admixed American	0.005%	20,001
Finnishnot grpmax-eligible	0.00469%	21,331
European (non-Finnish)	0.00407%	24,583
East Asian	0.00223%	44,872

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: UBAP1
Protein: p.Arg220Trp
Coding: c.658C>T
MANE Select: NM_016525
Type: single nucleotide variant
Location: chr9:34241683 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.60 · 3 PDB
Residue 220: a UniProt-annotated variant site (in spg80); a UniProt-annotated variant site (in spg80; uncertain significance)

Full UBAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UBAP1 p.Glu445Lys Uncertain significance ★★ ⚠ same condition
UBAP1 c.-104C>G Uncertain significance ★ same condition
UBAP1 c.-146G>T Uncertain significance ★ same condition
UBAP1 c.-167G>A Uncertain significance ★ same condition
UBAP1 c.-167G>C Uncertain significance ★ same condition
UBAP1 c.-167G>T Uncertain significance ★ same condition
UBAP1 c.-178G>A Uncertain significance ★ same condition
UBAP1 c.-181G>T 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/ubap1-p-arg220trp (accessed [today's date]).

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