Is POLI p.Ser142Arg (c.424A>C) pathogenic?

POLI p.Ser142Arg (c.424A>C) is classified Uncertain significance in POLI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.9335); Absent from gnomAD v4.1.

How common is POLI p.Ser142Arg (c.424A>C) in the general population?

POLI p.Ser142Arg (c.424A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about POLI p.Ser142Arg (c.424A>C)?

AlphaMissense predicts likely pathogenic (score 0.9335) — an in-silico prediction, not a clinical call.

POLI p.Ser142Arg

c.424A>C · rs2511483432 · VCV2609559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9335 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9335	likely pathogenic · top 5% in POLI
REVEL	0.678	pathogenic-leaning
SaProt	LLR -11.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 25 kb · p 0.092 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: POLI
Protein: p.Ser142Arg
Coding: c.424A>C
MANE Select: NM_007195
dbSNP: rs2511483432
Type: single nucleotide variant
Location: chr18:54277720 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.73 · 54 PDB
Residue 142: the umuc domain

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

Similar variants

POLI p.Ala23Thr Uncertain significance ★ ⚠ same type
POLI p.Ala351Ser Uncertain significance ★ ⚠ same type
POLI p.Ala564Asp Uncertain significance ★ ⚠ same type
POLI p.Arg126His Uncertain significance ★ ⚠ same type
POLI p.Arg126Pro Uncertain significance ★ ⚠ same type
POLI p.Arg373Gln Uncertain significance ★ ⚠ same type
POLI p.Arg382His Uncertain significance ★ same type
POLI p.Arg385Cys Uncertain significance ★ ⚠ 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/poli-p-ser142arg (accessed [today's date]).

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