Is UBAP1L p.Ser217Pro (c.649T>C) pathogenic?

UBAP1L p.Ser217Pro (c.649T>C) is classified Uncertain significance in UBAP1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.133); Very rare (popmax 0.000415%, nfe).

How common is UBAP1L p.Ser217Pro (c.649T>C) in the general population?

UBAP1L p.Ser217Pro (c.649T>C) is very rare (popmax 0.000415%, nfe) (gnomAD).

What do computational predictors say about UBAP1L p.Ser217Pro (c.649T>C)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

UBAP1L p.Ser217Pro

c.649T>C · VCV3464995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000415%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP -0.072, phastCons 0.98
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.29 · regional, not allelic
Overall
CADD	20.6	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 0.000415% European (non-Finnish) · 4/963,566 alleles

Filtering AF 9.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.6e-05%

Overall 0.000335% 4/1,194,844 alleles · very rare exomes 4/1,044,584 · genomes 0/150,260 · joint denominator

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: UBAP1L
Protein: p.Ser217Pro
Coding: c.649T>C
MANE Select: NM_001163692
Type: single nucleotide variant
Location: chr15:65102156 (GRCh38)
Gene constraint: LOEUF 1.548 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.48
Residue 217: the 'disordered' region

Full UBAP1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBAP1L c.910-7G>A Pathogenic/Likely pathogenic ★★ same type
UBAP1L c.120+1G>T Likely pathogenic ★ same type
UBAP1L c.121-2A>C Pathogenic ★ same type
UBAP1L p.Arg287Ter Pathogenic ★ same type
UBAP1L p.Ala115Val Uncertain significance ★ ⚠ same type
UBAP1L p.Ala156Ser Uncertain significance ★ ⚠ same type
UBAP1L p.Ala173Asp Uncertain significance ★ ⚠ same type
UBAP1L p.Ala183Glu 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/ubap1l-p-ser217pro (accessed [today's date]).

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