Is UBA7 p.Pro64Ser (c.190C>T) pathogenic?

UBA7 p.Pro64Ser (c.190C>T) is classified Uncertain significance in UBA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.0933); Ultra-rare (popmax 0.0165%, mid).

How common is UBA7 p.Pro64Ser (c.190C>T) in the general population?

UBA7 p.Pro64Ser (c.190C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about UBA7 p.Pro64Ser (c.190C>T)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

UBA7 p.Pro64Ser

c.190C>T · VCV4194704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.12	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 6.6	GERP 0.56, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 3,666 bp · p 1e-06 · regional, not allelic
Overall
CADD	22.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00155% 25/1,613,986 alleles · ultra-rare exomes 25/1,461,646 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0096%	10,418
Admixed American	0.00333%	30,015
European (non-Finnish)	0.00136%	73,752

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: UBA7
Protein: p.Pro64Ser
Coding: c.190C>T
MANE Select: NM_003335
Type: single nucleotide variant
Location: chr3:49813514 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 64: the '2 approximate repeats' region

Full UBA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBA7 p.Pro64Thr Uncertain significance ★ ⚠ same residue
UBA7 p.His817Arg Benign ★★ same type
UBA7 c.1904+3A>G Uncertain significance ★ same type
UBA7 p.Ala180Ser Uncertain significance ★ ⚠ same type
UBA7 p.Ala350Thr Uncertain significance ★ ⚠ same type
UBA7 p.Ala608Asp Uncertain significance ★ ⚠ same type
UBA7 p.Ala608Ser Uncertain significance ★ ⚠ same type
UBA7 p.Ala766Asp 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/uba7-p-pro64ser (accessed [today's date]).

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