Is UNC119 p.Val89= (c.267C>G) pathogenic?

UNC119 p.Val89= (c.267C>G) is classified Benign/Likely benign in UNC119 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). Rare (popmax 0.809%, mid); Associated with cone-rod dystrophy.

What condition is associated with UNC119 p.Val89= (c.267C>G)?

UNC119 p.Val89= (c.267C>G) is associated with cone-rod dystrophy (ClinVar).

How common is UNC119 p.Val89= (c.267C>G) in the general population?

UNC119 p.Val89= (c.267C>G) is rare (popmax 0.809%, mid) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

UNC119 p.Val89=

c.267C>G · rs145710399 · VCV322467

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.809%, mid)

Conditions

cone-rod dystrophy

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 7.5	GERP -0.33, phastCons 1
Overall
CADD	16.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.809% Middle Eastern · 49/6,058 alleles

Filtering AF 0.629% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.564%

Overall 0.0999% 1,613/1,614,176 alleles · rare exomes 1,477/1,461,828 · genomes 136/152,348 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.809%	124
Ashkenazi Jewishnot grpmax-eligible	0.385%	260
Remaining individualsnot grpmax-eligible	0.243%	411
Admixed American	0.235%	426
European (non-Finnish)	0.093%	1,076
African / African-American	0.0533%	1,877
South Asian	0.0165%	6,073
Finnishnot grpmax-eligible	0.00781%	12,806

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.Val89=
Coding: c.267C>G
MANE Select: NM_005148
dbSNP: rs145710399
Type: single nucleotide variant
Location: chr17:28548659 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 89: 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); a β-strand

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

Disease context

cone-rod dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

UNC119 p.Arg209His Uncertain significance ★★ ⚠ same condition
UNC119 p.Asp176Asn Uncertain significance ★★ ⚠ same condition
UNC119 p.Leu140Arg Uncertain significance ★★ ⚠ same condition
UNC119 c.220+15G>C Benign ★★ same condition
UNC119 c.437+7C>T Benign/Likely benign ★★ same condition
UNC119 c.*1C>T Benign/Likely benign ★★ same condition
UNC119 p.Arg119Gln Benign/Likely benign ★★ same condition
UNC119 p.Phe221= Benign/Likely benign ★★ 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/unc119-p-val89 (accessed [today's date]).

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