Is UTRN p.Arg520Cys (c.1558C>T) pathogenic?

UTRN p.Arg520Cys (c.1558C>T) is classified Uncertain significance in UTRN (ClinVar, Single submitter, 2 submitters; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1733); Ultra-rare (popmax 0.0416%, nfe).

How common is UTRN p.Arg520Cys (c.1558C>T) in the general population?

UTRN p.Arg520Cys (c.1558C>T) is ultra-rare (popmax 0.0416%, nfe) (gnomAD).

What do computational predictors say about UTRN p.Arg520Cys (c.1558C>T)?

AlphaMissense predicts likely benign (score 0.1733) — an in-silico prediction, not a clinical call.

UTRN p.Arg520Cys

c.1558C>T · rs147779975 · VCV2365475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1733	likely benign
REVEL	0.492	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 119 kb · p 0.35 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0416% European (non-Finnish) · 490/1,178,510 alleles

Filtering AF 0.0385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0373%

Overall 0.0325% 524/1,611,330 alleles · ultra-rare exomes 506/1,459,288 · genomes 18/152,042 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0416%	2,405
Middle Eastern	0.0329%	3,036
East Asian	0.0157%	6,379
Remaining individualsnot grpmax-eligible	0.0128%	7,787
Admixed American	0.00835%	11,975
African / African-American	0.00802%	12,465
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,516
South Asian	0.0033%	30,307
Finnishnot grpmax-eligible	0.00314%	31,894

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: UTRN
Protein: p.Arg520Cys
Coding: c.1558C>T
MANE Select: NM_007124
dbSNP: rs147779975
Type: single nucleotide variant
Location: chr6:144444326 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Residue 520: the 'interaction with synm' region

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

Similar variants

UTRN c.4437+9T>C Benign/Likely benign ★★ same type
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UTRN p.Arg1625Lys Likely benign ★★ same type
UTRN p.Arg1967Trp Benign/Likely benign ★★ same type
UTRN p.Gly1862Glu Likely benign ★★ same type
UTRN p.Ile2227Val Likely benign ★★ same type
UTRN p.Ser1561Cys Likely benign ★★ same type
UTRN p.Thr2288= Likely benign ★★ 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/utrn-p-arg520cys (accessed [today's date]).

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