Is UNC119 p.Arg225= (c.675G>T) pathogenic?

UNC119 p.Arg225= (c.675G>T) is classified Likely benign in UNC119 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-21). Ultra-rare (popmax 0.0395%, sas).

How common is UNC119 p.Arg225= (c.675G>T) in the general population?

UNC119 p.Arg225= (c.675G>T) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

UNC119 p.Arg225=

c.675G>T · rs572109137 · VCV1942607

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, 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 4	GERP 1.9, phastCons 1
Overall
CADD	10.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% South Asian · 36/91,080 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00248% 40/1,614,174 alleles · ultra-rare exomes 38/1,461,872 · genomes 2/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,530
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	8.47e-05%	1,180,012

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.Arg225=
Coding: c.675G>T
MANE Select: NM_005148
dbSNP: rs572109137
Type: single nucleotide variant
Location: chr17:28547345 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 225: 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 UniProt-annotated variant site (in cord24; uncertain significance); the 'required for centrosome localization' region; a β-strand

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

Similar variants

UNC119 p.Arg225Trp Uncertain significance ★★ same residue
UNC119 p.Arg225Gln 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
UNC119 p.Arg127His 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-arg225 (accessed [today's date]).

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