Is UTRN p.Ser1561Cys (c.4682C>G) pathogenic?

UTRN p.Ser1561Cys (c.4682C>G) is classified Likely benign in UTRN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0851); Low-frequency (popmax 1.35%, mid).

How common is UTRN p.Ser1561Cys (c.4682C>G) in the general population?

UTRN p.Ser1561Cys (c.4682C>G) is low-frequency (popmax 1.35%, mid) (gnomAD).

What do computational predictors say about UTRN p.Ser1561Cys (c.4682C>G)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

UTRN p.Ser1561Cys

c.4682C>G · rs35042870 · VCV715576

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.3, phastCons 0.9
Regional constraint	o/e 1.02	unconstrained · MANE · 119 kb · p 0.35 · regional, not allelic
Overall
CADD	23.1	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 1.35% Middle Eastern · 82/6,056 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.501% 8,083/1,613,880 alleles · low-frequency exomes 7,369/1,461,600 · genomes 714/152,280 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	4.84%	21
Amishnot grpmax-eligible	1.64%	61
Middle Easterngrpmax	1.35%	74
Remaining individualsnot grpmax-eligible	0.768%	130
South Asian	0.536%	187
European (non-Finnish)	0.444%	225
Admixed American	0.32%	313
Finnishnot grpmax-eligible	0.131%	762
African / African-American	0.0919%	1,088

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1561Cys
Coding: c.4682C>G
MANE Select: NM_007124
dbSNP: rs35042870
Type: single nucleotide variant
Location: chr6:144499345 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Residue 1561: the 'interaction with synm' region

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

Similar variants

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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.Thr2288= Likely benign ★★ same type
UTRN c.4134+1G>A Likely pathogenic ★ 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-ser1561cys (accessed [today's date]).

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