Is POLL p.Arg308Gln (c.923G>A) pathogenic?

POLL p.Arg308Gln (c.923G>A) is classified Uncertain significance in POLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1175); Ultra-rare (popmax 0.0379%, eas).

How common is POLL p.Arg308Gln (c.923G>A) in the general population?

POLL p.Arg308Gln (c.923G>A) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about POLL p.Arg308Gln (c.923G>A)?

AlphaMissense predicts likely benign (score 0.1175) — an in-silico prediction, not a clinical call.

POLL p.Arg308Gln

c.923G>A · rs764560391 · VCV3216374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1175 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1175	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -12.15	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 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,904 bp · p 0.00011 · regional, not allelic
Overall
CADD	28.7	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 0.0379% East Asian · 17/44,878 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.0018% 29/1,613,994 alleles · ultra-rare exomes 28/1,461,868 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,640
South Asian	0.0022%	45,543
Admixed American	0.00167%	59,996
African / African-American	0.00134%	74,898
European (non-Finnish)	0.000678%	147,504

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.Arg308Gln
Coding: c.923G>A
MANE Select: NM_001174084
dbSNP: rs764560391
Type: single nucleotide variant
Location: chr10:101583650 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.90 · 97 PDB
Residue 308: an α-helix

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

Similar variants

POLL p.Arg308Trp Uncertain significance ★ ⚠ same residue
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

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-arg308gln (accessed [today's date]).

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