Is UNC93B1 p.Pro402= (c.1206G>C) pathogenic?

UNC93B1 p.Pro402= (c.1206G>C) is classified Benign in UNC93B1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 7.49%, afr) — too common for a highly-penetrant pathogenic allele; Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with UNC93B1 p.Pro402= (c.1206G>C)?

UNC93B1 p.Pro402= (c.1206G>C) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

UNC93B1 p.Pro402=

Q: How common is UNC93B1 p.Pro402= (c.1206G>C) in the general population?

UNC93B1 p.Pro402= (c.1206G>C) is common (popmax 7.49%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1206G>C · rs112284414 · VCV470489

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.49%, afr) — too common for a highly-penetrant pathogenic allele

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.49% African / African-American · 5,457/72,850 alleles

Filtering AF 7.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.26%

Overall 1.2% 18,517/1,547,488 alleles · common exomes 14,518/1,395,612 · genomes 3,999/151,876 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.49%	13
South Asian	6.71%	15
East Asian	2.96%	34
Remaining individualsnot grpmax-eligible	1.45%	69
Admixed American	0.751%	133
Middle Eastern	0.689%	145
Ashkenazi Jewishnot grpmax-eligible	0.514%	195
European (non-Finnish)	0.416%	240
Finnishnot grpmax-eligible	0.0324%	3,091

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.Pro402=
Coding: c.1206G>C
MANE Select: NM_030930
dbSNP: rs112284414
Type: single nucleotide variant
Location: chr11:67995768 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.12 · 2 PDB
Residue 402: a turn

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 p.Pro402Leu Uncertain significance ★★ ⚠ same residue
UNC93B1 p.Pro402Arg Uncertain significance ★ ⚠ same residue
UNC93B1 p.Pro402Ser Likely benign ★ same residue
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

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-pro402 (accessed [today's date]).

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