Is UTRN p.Arg1541Ser (c.4623A>C) pathogenic?

UTRN p.Arg1541Ser (c.4623A>C) is classified Uncertain significance in UTRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: ambiguous (0.358); Very rare (popmax 0.00195%, nfe).

How common is UTRN p.Arg1541Ser (c.4623A>C) in the general population?

UTRN p.Arg1541Ser (c.4623A>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about UTRN p.Arg1541Ser (c.4623A>C)?

AlphaMissense predicts ambiguous (score 0.358) — an in-silico prediction, not a clinical call.

UTRN p.Arg1541Ser

c.4623A>C · VCV3814625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.358 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Computational evidence

Protein change
AlphaMissense	0.358	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -1.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 119 kb · p 0.35 · regional, not allelic
Overall
CADD	20.2	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 0.00195% European (non-Finnish) · 23/1,179,328 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00143% 23/1,613,146 alleles · very rare exomes 23/1,460,820 · genomes 0/152,326 · joint denominator

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.Arg1541Ser
Coding: c.4623A>C
MANE Select: NM_007124
Type: single nucleotide variant
Location: chr6:144499286 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Residue 1541: 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
UTRN c.4594-8C>T Benign/Likely benign ★★ same type
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-arg1541ser (accessed [today's date]).

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