Is UBA7 p.Val488Phe (c.1462G>T) pathogenic?

UBA7 p.Val488Phe (c.1462G>T) is classified Uncertain significance in UBA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-02). AlphaMissense: likely benign (0.1311); Ultra-rare (popmax 0.0494%, afr).

How common is UBA7 p.Val488Phe (c.1462G>T) in the general population?

UBA7 p.Val488Phe (c.1462G>T) is ultra-rare (popmax 0.0494%, afr) (gnomAD).

What do computational predictors say about UBA7 p.Val488Phe (c.1462G>T)?

AlphaMissense predicts likely benign (score 0.1311) — an in-silico prediction, not a clinical call.

UBA7 p.Val488Phe

c.1462G>T · VCV3330497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1311	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -13.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.4	GERP -3.4
Regional constraint	o/e 0.82	unconstrained · MANE · 3,666 bp · p 1e-06 · regional, not allelic
Overall
CADD	16.64	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 0.0494% African / African-American · 37/74,884 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00235% 38/1,613,966 alleles · ultra-rare exomes 16/1,461,864 · genomes 22/152,102 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0494%	2,024
Admixed American	0.00167%	59,992

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.Val488Phe
Coding: c.1462G>T
MANE Select: NM_003335
Type: single nucleotide variant
Location: chr3:49810522 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 488: the '2 approximate repeats' region; a UniProt-annotated variant site (found in a small consanguineous family with learning disability; uncertain significance)

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-val488phe (accessed [today's date]).

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