Is UNC93B1 p.Pro16= (c.48G>T) pathogenic?

UNC93B1 p.Pro16= (c.48G>T) is classified Likely benign in UNC93B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Very rare (popmax 0.00447%, afr); Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with UNC93B1 p.Pro16= (c.48G>T)?

UNC93B1 p.Pro16= (c.48G>T) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

How common is UNC93B1 p.Pro16= (c.48G>T) in the general population?

UNC93B1 p.Pro16= (c.48G>T) is very rare (popmax 0.00447%, afr) (gnomAD).

UNC93B1 p.Pro16=

c.48G>T · rs1343235751 · VCV2048129

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00447%, afr)

Conditions

herpes simplex encephalitis, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.99	GERP -2.1
Overall
CADD	6.305	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% African / African-American · 3/67,094 alleles

Filtering AF 0.00119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000629%

Overall 0.000785% 11/1,401,282 alleles · very rare exomes 7/1,249,468 · genomes 4/151,814 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00447%	22,365
Remaining individualsnot grpmax-eligible	0.00189%	52,776
European (non-Finnish)	0.000651%	153,524

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: UNC93B1
Protein: p.Pro16=
Coding: c.48G>T
MANE Select: NM_030930
dbSNP: rs1343235751
Type: single nucleotide variant
Location: chr11:68003996 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.12 · 2 PDB
Residue 16: the 'disordered' region

Full UNC93B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

herpes simplex encephalitis, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC93B1 c.1090-5C>A Uncertain significance ★★ same condition
UNC93B1 c.1363+4A>C Uncertain significance ★★ same condition
UNC93B1 p.Ala13Thr Uncertain significance ★★ ⚠ same condition
UNC93B1 p.Ala214Pro Uncertain significance ★★ ⚠ same condition
UNC93B1 p.Ala214Thr Uncertain significance ★★ ⚠ same condition
UNC93B1 p.Ala214Val Uncertain significance ★★ ⚠ same condition
UNC93B1 p.Ala233Thr Uncertain significance ★★ ⚠ same condition
UNC93B1 p.Arg157His Uncertain significance ★★ ⚠ same condition

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/unc93b1-p-pro16 (accessed [today's date]).

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