Is UNC119 p.Arg94Pro (c.281G>C) pathogenic?

UNC119 p.Arg94Pro (c.281G>C) is classified Uncertain significance in UNC119 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-05). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1.

How common is UNC119 p.Arg94Pro (c.281G>C) in the general population?

UNC119 p.Arg94Pro (c.281G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC119 p.Arg94Pro (c.281G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

UNC119 p.Arg94Pro

c.281G>C · rs763481567 · VCV1493362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 5% in UNC119
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -17.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.35, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,257 bp · p 0.44 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UNC119
Protein: p.Arg94Pro
Coding: c.281G>C
MANE Select: NM_005148
dbSNP: rs763481567
Type: single nucleotide variant
Location: chr17:28548645 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 94: 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

Similar variants

UNC119 p.Arg94Trp Uncertain significance ★★ ⚠ same residue
UNC119 p.Arg94Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
UNC119 p.Arg94Leu 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-arg94pro (accessed [today's date]).

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