Is UTP20 p.Arg2005His (c.6014G>A) pathogenic?

UTP20 p.Arg2005His (c.6014G>A) is classified Uncertain significance in UTP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1104); Very rare (popmax 0.00168%, amr).

How common is UTP20 p.Arg2005His (c.6014G>A) in the general population?

UTP20 p.Arg2005His (c.6014G>A) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about UTP20 p.Arg2005His (c.6014G>A)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

UTP20 p.Arg2005His

c.6014G>A · rs756559736 · VCV3187940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.35	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 90 kb · p 0.01 · regional, not allelic
Overall
CADD	27.3	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 0.00168% Admixed American · 1/59,614 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000868% 14/1,612,204 alleles · very rare exomes 11/1,460,208 · genomes 3/151,996 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,212
Admixed Americangrpmax	0.00168%	59,614
South Asian	0.0011%	90,632
European (non-Finnish)	0.000848%	117,952

Remaining individuals 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: UTP20
Protein: p.Arg2005His
Coding: c.6014G>A
MANE Select: NM_014503
dbSNP: rs756559736
Type: single nucleotide variant
Location: chr12:101365514 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI <0.01 (gnomAD)
Residue 2005: an α-helix

Full UTP20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UTP20 p.Arg2005Cys Uncertain significance ★ same residue
UTP20 p.Ile1931Thr Uncertain significance ★★ same type
UTP20 c.735+8A>C Benign ★★ same type
UTP20 p.Ala2599= Benign/Likely benign ★★ same type
UTP20 p.His1302= Benign ★★ same type
UTP20 p.His1934Arg Benign ★★ same type
UTP20 p.His304= Benign ★★ same type
UTP20 p.Leu2053= 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/utp20-p-arg2005his (accessed [today's date]).

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