Is UNC119 p.Ala13= (c.39G>A) pathogenic?

UNC119 p.Ala13= (c.39G>A) is classified Conflicting classifications of pathogenicity in UNC119 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-02). Very rare (popmax 0.00844%, nfe); Associated with cone-rod dystrophy.

What condition is associated with UNC119 p.Ala13= (c.39G>A)?

UNC119 p.Ala13= (c.39G>A) is associated with cone-rod dystrophy (ClinVar).

How common is UNC119 p.Ala13= (c.39G>A) in the general population?

UNC119 p.Ala13= (c.39G>A) is very rare (popmax 0.00844%, nfe) (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.Ala13=

c.39G>A · rs749427491 · VCV889006

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00844%, nfe)

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 2.5	GERP 0.14, phastCons 1
Overall
CADD	13.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00844% European (non-Finnish) · 98/1,160,462 alleles

Filtering AF 0.00709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00651%

Overall 0.00656% 102/1,553,838 alleles · very rare exomes 102/1,401,608 · genomes 0/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00844%	11,841
Remaining individualsnot grpmax-eligible	0.00662%	15,094

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.Ala13=
Coding: c.39G>A
MANE Select: NM_005148
dbSNP: rs749427491
Type: single nucleotide variant
Location: chr17:28552519 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 13: the 'disordered' region; the 'required for midbody localization' region

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-ala13 (accessed [today's date]).

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