Is POLL p.Arg386His (c.1157G>A) pathogenic?

POLL p.Arg386His (c.1157G>A) is classified Uncertain significance in POLL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: ambiguous (0.3581); Very rare (popmax 0.00831%, nfe).

How common is POLL p.Arg386His (c.1157G>A) in the general population?

POLL p.Arg386His (c.1157G>A) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about POLL p.Arg386His (c.1157G>A)?

AlphaMissense predicts ambiguous (score 0.3581) — an in-silico prediction, not a clinical call.

POLL p.Arg386His

c.1157G>A · VCV3781657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3581	ambiguous
REVEL	0.481	indeterminate
SaProt	LLR -12.15	damaging
Splicing
SpliceAI	Δ0.42	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,904 bp · p 0.00011 · regional, not allelic
Overall
CADD	33.0	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 0.00831% European (non-Finnish) · 98/1,179,980 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00638% 103/1,614,156 alleles · very rare exomes 98/1,461,812 · genomes 5/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,041
Remaining individualsnot grpmax-eligible	0.0048%	20,836
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.0011%	91,086

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.Arg386His
Coding: c.1157G>A
MANE Select: NM_001174084
Type: single nucleotide variant
Location: chr10:101582800 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.90 · 97 PDB
Residue 386: a binding site

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

Similar variants

POLL p.Arg386Cys 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-arg386his (accessed [today's date]).

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