Is UBAP2 p.Ser439Arg (c.1317C>G) pathogenic?

UBAP2 p.Ser439Arg (c.1317C>G) is classified Uncertain significance in UBAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely pathogenic (0.6109); Ultra-rare (popmax 0.0267%, afr).

How common is UBAP2 p.Ser439Arg (c.1317C>G) in the general population?

UBAP2 p.Ser439Arg (c.1317C>G) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about UBAP2 p.Ser439Arg (c.1317C>G)?

AlphaMissense predicts likely pathogenic (score 0.6109) — an in-silico prediction, not a clinical call.

UBAP2 p.Ser439Arg

c.1317C>G · VCV4194801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6109	likely pathogenic
REVEL	0.117	moderately benign-leaning
SaProt	LLR -8.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 95 kb · p 0.96 · regional, not allelic
Overall
CADD	24.5	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 0.0267% African / African-American · 20/74,888 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,613,962 alleles · ultra-rare exomes 7/1,461,866 · genomes 14/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,744
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: UBAP2
Protein: p.Ser439Arg
Coding: c.1317C>G
MANE Select: NM_001370062
Type: single nucleotide variant
Location: chr9:33944593 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.47
Residue 439: a modified residue (phosphoserine); the 'disordered' region

Full UBAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBAP2 p.Leu667Ile Benign ★★ same type
UBAP2 p.Met762Ile Benign ★★ same type
UBAP2 p.Ala1070Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala217Ser Uncertain significance ★ ⚠ same type
UBAP2 p.Ala305Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala382Thr Uncertain significance ★ ⚠ same type
UBAP2 p.Ala849Val Uncertain significance ★ ⚠ same type
UBAP2 p.Ala851Val Uncertain significance ★ ⚠ 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/ubap2-p-ser439arg (accessed [today's date]).

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