Is UNC93B1 p.Pro400= (c.1200A>G) pathogenic?

UNC93B1 p.Pro400= (c.1200A>G) is classified Likely benign in UNC93B1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-02). Ultra-rare (popmax 0.0617%, afr); Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with UNC93B1 p.Pro400= (c.1200A>G)?

UNC93B1 p.Pro400= (c.1200A>G) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

How common is UNC93B1 p.Pro400= (c.1200A>G) in the general population?

UNC93B1 p.Pro400= (c.1200A>G) is ultra-rare (popmax 0.0617%, afr) (gnomAD).

UNC93B1 p.Pro400=

c.1200A>G · rs774307547 · VCV1146938

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, 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 -15
Overall
CADD	0.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0617% African / African-American · 45/72,982 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00317% 49/1,548,080 alleles · ultra-rare exomes 20/1,396,082 · genomes 29/151,998 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0617%	1,622
Admixed American	0.00392%	25,502
Remaining individualsnot grpmax-eligible	0.00334%	29,955

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.Pro400=
Coding: c.1200A>G
MANE Select: NM_030930
dbSNP: rs774307547
Type: single nucleotide variant
Location: chr11:67995774 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.12 · 2 PDB

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-pro400 (accessed [today's date]).

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