Is UBA7 p.Phe704Ser (c.2111T>C) pathogenic?

UBA7 p.Phe704Ser (c.2111T>C) is classified Uncertain significance in UBA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.6906); Very rare (popmax 8.47e-05%, nfe).

How common is UBA7 p.Phe704Ser (c.2111T>C) in the general population?

UBA7 p.Phe704Ser (c.2111T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about UBA7 p.Phe704Ser (c.2111T>C)?

AlphaMissense predicts likely pathogenic (score 0.6906) — an in-silico prediction, not a clinical call.

UBA7 p.Phe704Ser

c.2111T>C · VCV4601127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6906 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6906	likely pathogenic · top 7% in UBA7
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -15.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,757 bp · p 0.2 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.2e-05% 1/1,614,058 alleles · very rare exomes 0/1,461,866 · genomes 1/152,192 · joint denominator

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.Phe704Ser
Coding: c.2111T>C
MANE Select: NM_003335
Type: single nucleotide variant
Location: chr3:49809442 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 704: a UniProt-annotated variant site (found in a small consanguineous family with learning disability; uncertain significance); a β-strand

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-phe704ser (accessed [today's date]).

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