Is UTRN p.Arg2279Ser (c.6835C>A) pathogenic?

UTRN p.Arg2279Ser (c.6835C>A) is classified Uncertain significance in UTRN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-05). AlphaMissense: likely pathogenic (0.9706); Ultra-rare (popmax 0.0681%, afr).

How common is UTRN p.Arg2279Ser (c.6835C>A) in the general population?

UTRN p.Arg2279Ser (c.6835C>A) is ultra-rare (popmax 0.0681%, afr) (gnomAD).

What do computational predictors say about UTRN p.Arg2279Ser (c.6835C>A)?

AlphaMissense predicts likely pathogenic (score 0.9706) — an in-silico prediction, not a clinical call.

UTRN p.Arg2279Ser

c.6835C>A · rs114254210 · VCV2351328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, afr)

Computational evidence

Protein change
AlphaMissense	0.9706	likely pathogenic · top 6% in UTRN
REVEL	0.326	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 302 kb · p 0.00016 · regional, not allelic
Overall
CADD	28.5	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 0.0681% African / African-American · 51/74,838 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.0036% 58/1,610,856 alleles · ultra-rare exomes 26/1,458,662 · genomes 32/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0681%	1,467
Middle Eastern	0.0166%	6,040
Remaining individualsnot grpmax-eligible	0.00641%	15,590
Admixed American	0.00338%	29,563

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.Arg2279Ser
Coding: c.6835C>A
MANE Select: NM_007124
dbSNP: rs114254210
Type: single nucleotide variant
Location: chr6:144550989 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)

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-arg2279ser (accessed [today's date]).

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