Is UNC119 p.Arg168= (c.504C>T) pathogenic?

UNC119 p.Arg168= (c.504C>T) is classified Likely benign in UNC119 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). Ultra-rare (popmax 0.0176%, sas).

How common is UNC119 p.Arg168= (c.504C>T) in the general population?

UNC119 p.Arg168= (c.504C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

UNC119 p.Arg168=

c.504C>T · rs765311171 · VCV1139115

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

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 0.11	GERP -3.9, phastCons 0.89
Overall
CADD	6.726	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,088 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00105% 17/1,614,198 alleles · ultra-rare exomes 17/1,461,888 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,693
Middle Eastern	0.0165%	6,062

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: UNC119
Protein: p.Arg168=
Coding: c.504C>T
MANE Select: NM_005148
dbSNP: rs765311171
Type: single nucleotide variant
Location: chr17:28547783 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 168: a UniProt-annotated variant site (in cord24; when expressed in transgenic mice, it results in age-dependent fundus lesions, defects in photoreceptor synaptic transmission and retinal degeneration); the 'required for centrosome localization' region

Full UNC119 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UNC119 p.Arg168Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
UNC119 p.Arg168His Uncertain significance ★ ⚠ same residue
UNC119 p.Arg168Leu Uncertain significance ★ ⚠ same residue
UNC119 p.Arg113Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg118Gln Uncertain significance ★★ ⚠ same type
UNC119 p.Arg118Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg119Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg127Cys Uncertain significance ★★ ⚠ same type

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/unc119-p-arg168 (accessed [today's date]).

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