Is USE1 p.Ala173Val (c.518C>T) pathogenic?

USE1 p.Ala173Val (c.518C>T) is classified Uncertain significance in USE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: ambiguous (0.4245); Very rare (popmax 0.00893%, eas).

How common is USE1 p.Ala173Val (c.518C>T) in the general population?

USE1 p.Ala173Val (c.518C>T) is very rare (popmax 0.00893%, eas) (gnomAD).

What do computational predictors say about USE1 p.Ala173Val (c.518C>T)?

AlphaMissense predicts ambiguous (score 0.4245) — an in-silico prediction, not a clinical call.

USE1 p.Ala173Val

c.518C>T · rs201641941 · VCV2463813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Computational evidence

Protein change
AlphaMissense	0.4245	ambiguous
REVEL	0.375	indeterminate
SaProt	LLR -10.47	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.69, phastCons 1
Overall
CADD	28.4	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 0.00893% East Asian · 4/44,772 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00267% 43/1,611,738 alleles · very rare exomes 40/1,459,680 · genomes 3/152,058 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,193
Admixed American	0.00503%	19,878
Remaining individualsnot grpmax-eligible	0.00481%	20,805
Finnishnot grpmax-eligible	0.00313%	31,945
African / African-American	0.00267%	37,443
European (non-Finnish)	0.00246%	40,655

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: USE1
Protein: p.Ala173Val
Coding: c.518C>T
MANE Select: NM_018467
dbSNP: rs201641941
Type: single nucleotide variant
Location: chr19:17219308 (GRCh38)
Structure: AlphaFold pLDDT 82.49 · 5 PDB
Residue 173: the ubc core domain; a turn

Full USE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBE2Z p.Arg245Gln Uncertain significance ★ same type
UBE2Z p.Arg289His Uncertain significance ★ same type
UBE2Z p.Asn180Asp Uncertain significance ★ ⚠ same type
UBE2Z p.Gln298Lys Uncertain significance ★ ⚠ same type
UBE2Z p.Glu265Lys Uncertain significance ★ ⚠ same type
UBE2Z p.His132Asp Uncertain significance ★ ⚠ same type
UBE2Z p.His329Arg Uncertain significance ★ ⚠ same type
UBE2Z p.Val121Ile 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/use1-p-ala173val (accessed [today's date]).

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