Is UBA7 p.Pro595Ser (c.1783C>T) pathogenic?

UBA7 p.Pro595Ser (c.1783C>T) is classified Likely benign in UBA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). AlphaMissense: likely benign (0.0669); Ultra-rare (popmax 0.0164%, mid).

How common is UBA7 p.Pro595Ser (c.1783C>T) in the general population?

UBA7 p.Pro595Ser (c.1783C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about UBA7 p.Pro595Ser (c.1783C>T)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

UBA7 p.Pro595Ser

c.1783C>T · rs1025059270 · VCV2220046

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.62	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 -2.3	GERP -3.4
Regional constraint	o/e 0.94	unconstrained · MANE · 4,757 bp · p 0.2 · regional, not allelic
Overall
CADD	0.092	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00198% 32/1,613,672 alleles · ultra-rare exomes 28/1,461,536 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00878%	11,386
African / African-American	0.00267%	37,457
European (non-Finnish)	0.00178%	56,191

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.Pro595Ser
Coding: c.1783C>T
MANE Select: NM_003335
dbSNP: rs1025059270
Type: single nucleotide variant
Location: chr3:49810034 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 595: a UniProt-annotated variant site (found in a small consanguineous family with learning disability; uncertain significance); an α-helix

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

Similar variants

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
UBA7 p.Ala823Val 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-pro595ser (accessed [today's date]).

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