Is POLL p.Ile491Val (c.1471A>G) pathogenic?

POLL p.Ile491Val (c.1471A>G) is classified Likely benign in POLL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-30). AlphaMissense: likely benign (0.0929); Rare (popmax 0.387%, afr); Associated with POLL-related disorder.

What condition is associated with POLL p.Ile491Val (c.1471A>G)?

POLL p.Ile491Val (c.1471A>G) is associated with POLL-related disorder (ClinVar).

How common is POLL p.Ile491Val (c.1471A>G) in the general population?

POLL p.Ile491Val (c.1471A>G) is rare (popmax 0.387%, afr) (gnomAD).

What do computational predictors say about POLL p.Ile491Val (c.1471A>G)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

POLL p.Ile491Val

c.1471A>G · rs138242344 · VCV3041609

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.387%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

POLL-related disorder

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -8.28	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 1.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,904 bp · p 0.00011 · regional, not allelic
Overall
CADD	16.86	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 0.387% African / African-American · 290/75,014 alleles

Filtering AF 0.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.0196% 317/1,613,750 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.387%	259
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Admixed American	0.0183%	5,455
East Asian	0.00223%	44,830
South Asian	0.0011%	91,072
European (non-Finnish)	8.47e-05%	1,179,979

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.Ile491Val
Coding: c.1471A>G
MANE Select: NM_001174084
dbSNP: rs138242344
Type: single nucleotide variant
Location: chr10:101579710 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.90 · 97 PDB
Residue 491: the 'dna-binding' region; a β-strand

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

Disease context

POLL-related disorder

Similar variants

POLL p.Gln120= Likely benign same condition
POLL p.Ser497Arg Likely benign same condition
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

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-ile491val (accessed [today's date]).

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