Is UTRN p.Ala709Asp (c.2126C>A) pathogenic?

UTRN p.Ala709Asp (c.2126C>A) is classified Uncertain significance in UTRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.1544); Absent from gnomAD v4.1.

How common is UTRN p.Ala709Asp (c.2126C>A) in the general population?

UTRN p.Ala709Asp (c.2126C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UTRN p.Ala709Asp (c.2126C>A)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

UTRN p.Ala709Asp

c.2126C>A · VCV4603398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.263	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 0.56	GERP 1.2, phastCons 0.99
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

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UTRN
Protein: p.Ala709Asp
Coding: c.2126C>A
MANE Select: NM_007124
Type: single nucleotide variant
Location: chr6:144451423 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Residue 709: the 'interaction with synm' region

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

Similar variants

UTRN p.Ala709Thr Uncertain significance ★ ⚠ same residue
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

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-ala709asp (accessed [today's date]).

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