Is UTRN p.Val93Ile (c.277G>A) pathogenic?

UTRN p.Val93Ile (c.277G>A) is classified Uncertain significance in UTRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely benign (0.1009); Ultra-rare (popmax 0.0121%, sas).

How common is UTRN p.Val93Ile (c.277G>A) in the general population?

UTRN p.Val93Ile (c.277G>A) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about UTRN p.Val93Ile (c.277G>A)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

UTRN p.Val93Ile

c.277G>A · VCV3467497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.764	pathogenic-leaning
SaProt	—	not scored · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.94, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 138 kb · p 0.00042 · regional, not allelic
Overall
CADD	29.5	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 0.0121% South Asian · 11/91,090 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00427% 69/1,614,082 alleles · ultra-rare exomes 59/1,461,882 · genomes 10/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,281
East Asian	0.00891%	11,223
Remaining individualsnot grpmax-eligible	0.008%	12,498
African / African-American	0.004%	24,973
European (non-Finnish)	0.00381%	26,223
Finnishnot grpmax-eligible	0.00156%	64,022

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.Val93Ile
Coding: c.277G>A
MANE Select: NM_007124
Type: single nucleotide variant
Location: chr6:144423591 (GRCh38)
Gene constraint: LOEUF 0.665 · pLI <0.01 (gnomAD)
Residue 93: the calponin-homology (ch) 1 domain; the 'actin-binding' region; an α-helix

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-val93ile (accessed [today's date]).

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