Is POLL p.Arg123Lys (c.368G>A) pathogenic?

POLL p.Arg123Lys (c.368G>A) is classified Uncertain significance in POLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: likely benign (0.0876); Very rare (popmax 0.00224%, eas).

How common is POLL p.Arg123Lys (c.368G>A) in the general population?

POLL p.Arg123Lys (c.368G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about POLL p.Arg123Lys (c.368G>A)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

POLL p.Arg123Lys

c.368G>A · VCV4141342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.6, phastCons 0.98
Regional constraint	o/e 0.86	unconstrained · MANE · 7,904 bp · p 0.00011 · regional, not allelic
Overall
CADD	14.59	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,614 alleles

Overall 0.000207% 3/1,451,394 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,614
Remaining individualsnot grpmax-eligible	0.00161%	62,002
European (non-Finnish)	8.54e-05%	1,171,302

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.Arg123Lys
Coding: c.368G>A
MANE Select: NM_001174084
Type: single nucleotide variant
Location: chr10:101585904 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.90 · 97 PDB
Residue 123: 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-arg123lys (accessed [today's date]).

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