Is UBAP1 p.Arg77Trp (c.229C>T) pathogenic?

UBAP1 p.Arg77Trp (c.229C>T) is classified Uncertain significance in UBAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.1163); Very rare (popmax 0.0028%, afr); Associated with Inborn genetic diseases.

What condition is associated with UBAP1 p.Arg77Trp (c.229C>T)?

UBAP1 p.Arg77Trp (c.229C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UBAP1 p.Arg77Trp (c.229C>T) in the general population?

UBAP1 p.Arg77Trp (c.229C>T) is very rare (popmax 0.0028%, afr) (gnomAD).

What do computational predictors say about UBAP1 p.Arg77Trp (c.229C>T)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

UBAP1 p.Arg77Trp

c.229C>T · VCV3464985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.73	GERP -0.014
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 0.0029 · regional, not allelic
Overall
CADD	16.72	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% African / African-American · 2/71,544 alleles

Filtering AF 0.000464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000174%

Overall 0.000467% 7/1,500,536 alleles · very rare exomes 7/1,348,296 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0028%	35,772
East Asian	0.00228%	43,834
Remaining individualsnot grpmax-eligible	0.00174%	57,582
European (non-Finnish)	0.000266%	375,284

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.Arg77Trp
Coding: c.229C>T
MANE Select: NM_016525
Type: single nucleotide variant
Location: chr9:34241254 (GRCh38)
Gene constraint: LOEUF 0.285 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.60 · 3 PDB
Residue 77: the 'interaction with escrt-i' region

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
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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-arg77trp (accessed [today's date]).

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