Is UNC79 p.Ile2197= (c.6591C>T) pathogenic?

UNC79 p.Ile2197= (c.6591C>T) is classified Likely benign in UNC79 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-26). Rare (popmax 0.1%, afr); Associated with UNC79-related disorder.

What condition is associated with UNC79 p.Ile2197= (c.6591C>T)?

UNC79 p.Ile2197= (c.6591C>T) is associated with UNC79-related disorder (ClinVar).

How common is UNC79 p.Ile2197= (c.6591C>T) in the general population?

UNC79 p.Ile2197= (c.6591C>T) is rare (popmax 0.1%, afr) (gnomAD).

UNC79 p.Ile2197=

c.6591C>T · VCV3352515

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.1%, afr)

Conditions

UNC79-related disorder

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 -5.4	GERP -4.3
Overall
CADD	0.671	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% African / African-American · 75/74,920 alleles

Filtering AF 0.0818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0751%

Overall 0.00688% 111/1,613,980 alleles · rare exomes 60/1,461,858 · genomes 51/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	999
Admixed American	0.0217%	4,615
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00144%	69,411
South Asian	0.0011%	91,082

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: UNC79
Protein: p.Ile2197=
Coding: c.6591C>T
MANE Select: NM_001395159
Type: single nucleotide variant
Location: chr14:93654001 (GRCh38)
Gene constraint: LOEUF 0.168 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.95 · 3 PDB
Residue 2197: an α-helix

Full UNC79 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UNC79-related disorder

Similar variants

UNC79 p.Ile1680Thr Uncertain significance ★★ same condition
UNC79 p.Trp255Ter Pathogenic ★ same condition
UNC79 p.Arg1332Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
UNC79 p.Arg747Ter Uncertain significance ★ same condition
UNC79 p.Gln2472Ter Uncertain significance ★ same condition
UNC79 p.Ile505Val Uncertain significance ★ same condition
UNC79 p.Pro1278Ser Uncertain significance ★ same condition
UNC79 c.1052+2T>A 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/unc79-p-ile2197 (accessed [today's date]).

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