Is UTP20 p.Pro856Ser (c.2566C>T) pathogenic?

UTP20 p.Pro856Ser (c.2566C>T) is classified Uncertain significance in UTP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1518); Very rare (popmax 0.00833%, amr).

How common is UTP20 p.Pro856Ser (c.2566C>T) in the general population?

UTP20 p.Pro856Ser (c.2566C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about UTP20 p.Pro856Ser (c.2566C>T)?

AlphaMissense predicts likely benign (score 0.1518) — an in-silico prediction, not a clinical call.

UTP20 p.Pro856Ser

c.2566C>T · rs1291147923 · VCV2238735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1518	likely benign
REVEL	0.09	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 4.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 90 kb · p 0.01 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00833% Admixed American · 5/59,998 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000372% 6/1,613,940 alleles · very rare exomes 6/1,461,718 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
European (non-Finnish)	8.48e-05%	1,179,930

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.Pro856Ser
Coding: c.2566C>T
MANE Select: NM_014503
dbSNP: rs1291147923
Type: single nucleotide variant
Location: chr12:101317491 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI <0.01 (gnomAD)

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

Similar variants

UTP20 p.Pro856Leu 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-pro856ser (accessed [today's date]).

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