Is POLL p.Arg45Trp (c.133C>T) pathogenic?

POLL p.Arg45Trp (c.133C>T) is classified Uncertain significance in POLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.1159); Ultra-rare (popmax 0.0648%, sas).

How common is POLL p.Arg45Trp (c.133C>T) in the general population?

POLL p.Arg45Trp (c.133C>T) is ultra-rare (popmax 0.0648%, sas) (gnomAD).

What do computational predictors say about POLL p.Arg45Trp (c.133C>T)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

POLL p.Arg45Trp

c.133C>T · VCV4141329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0648%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -10.25	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.1, phastCons 0.076
Regional constraint	o/e 0.86	unconstrained · MANE · 7,904 bp · p 0.00011 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0648% South Asian · 59/91,018 alleles

Filtering AF 0.0515% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0468%

Overall 0.00701% 113/1,611,928 alleles · ultra-rare exomes 103/1,459,598 · genomes 10/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0648%	1,543
East Asian	0.0446%	2,241
Admixed American	0.00333%	29,990
Remaining individualsnot grpmax-eligible	0.0032%	31,211
European (non-Finnish)	0.00255%	39,293

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: POLL
Protein: p.Arg45Trp
Coding: c.133C>T
MANE Select: NM_001174084
Type: single nucleotide variant
Location: chr10:101586139 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.90 · 97 PDB
Residue 45: the brct domain

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

Similar variants

POLL c.1066-135C>A Benign ★★ same type
POLL c.1195-62A>G Benign ★★ same type
POLL c.1195-6T>C Benign ★★ same type
POLL c.573+42A>G Benign ★★ same type
POLL c.892-76T>C Benign ★★ same type
POLL c.892-95T>C Benign ★★ same type
POLL c.*68C>T Benign ★★ same type
POLL p.Arg438Trp 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/poll-p-arg45trp (accessed [today's date]).

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