Is UNC93B1 p.Phe232= (c.696C>T) pathogenic?

UNC93B1 p.Phe232= (c.696C>T) is classified Likely benign in UNC93B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). Ultra-rare (popmax 0.02%, amr); Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with UNC93B1 p.Phe232= (c.696C>T)?

UNC93B1 p.Phe232= (c.696C>T) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

How common is UNC93B1 p.Phe232= (c.696C>T) in the general population?

UNC93B1 p.Phe232= (c.696C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

UNC93B1 p.Phe232=

c.696C>T · rs766090062 · VCV1565347

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

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 -1.8
Overall
CADD	8.699	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,012 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00285% 46/1,613,794 alleles · ultra-rare exomes 44/1,461,572 · genomes 2/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,001
East Asian	0.00891%	11,225
Remaining individualsnot grpmax-eligible	0.0032%	31,229
European (non-Finnish)	0.00229%	43,698
South Asian	0.0011%	91,078

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.Phe232=
Coding: c.696C>T
MANE Select: NM_030930
dbSNP: rs766090062
Type: single nucleotide variant
Location: chr11:67998444 (GRCh38)
Gene constraint: LOEUF 1.059 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.12 · 2 PDB
Residue 232: an α-helix

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-phe232 (accessed [today's date]).

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