Is UBA7 p.Ser70Pro (c.208T>C) pathogenic?

UBA7 p.Ser70Pro (c.208T>C) is classified Uncertain significance in UBA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: likely benign (0.0843); Ultra-rare (popmax 0.0417%, amr).

How common is UBA7 p.Ser70Pro (c.208T>C) in the general population?

UBA7 p.Ser70Pro (c.208T>C) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about UBA7 p.Ser70Pro (c.208T>C)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

UBA7 p.Ser70Pro

c.208T>C · rs765726926 · VCV2403586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -7.72	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 0.61	GERP -2, phastCons 0.96
Regional constraint	o/e 0.82	unconstrained · MANE · 3,666 bp · p 1e-06 · regional, not allelic
Overall
CADD	17.24	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 0.0417% Admixed American · 25/60,010 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00824% 133/1,613,736 alleles · ultra-rare exomes 114/1,461,516 · genomes 19/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0176%	5,679
European (non-Finnish)	0.00797%	12,553
African / African-American	0.00133%	74,924

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.Ser70Pro
Coding: c.208T>C
MANE Select: NM_003335
dbSNP: rs765726926
Type: single nucleotide variant
Location: chr3:49813496 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 70: an α-helix; the '2 approximate repeats' region

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-ser70pro (accessed [today's date]).

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