Is UBAP2 p.Phe425Leu (c.1273T>C) pathogenic?

UBAP2 p.Phe425Leu (c.1273T>C) is classified Uncertain significance in UBAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely pathogenic (0.66); Ultra-rare (popmax 0.0134%, afr).

How common is UBAP2 p.Phe425Leu (c.1273T>C) in the general population?

UBAP2 p.Phe425Leu (c.1273T>C) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about UBAP2 p.Phe425Leu (c.1273T>C)?

AlphaMissense predicts likely pathogenic (score 0.66) — an in-silico prediction, not a clinical call.

UBAP2 p.Phe425Leu

c.1273T>C · VCV4194794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.66 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.66	likely pathogenic
REVEL	0.116	moderately benign-leaning
SaProt	LLR -4.50	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 9.3	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 95 kb · p 0.96 · regional, not allelic
Overall
CADD	23.2	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 0.0134% African / African-American · 10/74,854 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000683% 11/1,611,366 alleles · ultra-rare exomes 8/1,459,184 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,485
European (non-Finnish)	8.49e-05%	1,177,812

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.Phe425Leu
Coding: c.1273T>C
MANE Select: NM_001370062
Type: single nucleotide variant
Location: chr9:33944637 (GRCh38)
Gene constraint: LOEUF 0.625 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.47
Residue 425: 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-phe425leu (accessed [today's date]).

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