Is CHRNA2 p.Ser482Pro (c.1444T>C) pathogenic?

CHRNA2 p.Ser482Pro (c.1444T>C) is classified Uncertain significance in CHRNA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-25). AlphaMissense: likely pathogenic (0.8508); Absent from gnomAD v4.1.

How common is CHRNA2 p.Ser482Pro (c.1444T>C) in the general population?

CHRNA2 p.Ser482Pro (c.1444T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNA2 p.Ser482Pro (c.1444T>C)?

AlphaMissense predicts likely pathogenic (score 0.8508) — an in-silico prediction, not a clinical call.

CHRNA2 p.Ser482Pro

c.1444T>C · rs2132650030 · VCV1314225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8508 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8508	likely pathogenic
REVEL	0.241	benign-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.53	GERP -2.2
Regional constraint	o/e 1.05	unconstrained · MANE · 1,855 bp · p 0.38 · regional, not allelic
Overall
CADD	12.09	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

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: CHRNA2
Protein: p.Ser482Pro
Coding: c.1444T>C
MANE Select: NM_000742
dbSNP: rs2132650030
Type: single nucleotide variant
Location: chr8:27462999 (GRCh38)
Gene constraint: LOEUF 1.195 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.88 · 1 PDB

Full CHRNA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNA2 c.1464+4C>T Uncertain significance ★★ same type
CHRNA2 c.1464+5G>A Uncertain significance ★★ same type
CHRNA2 c.294+1G>A Uncertain significance ★★ same type
CHRNA2 c.294+5G>A Uncertain significance ★★ same type
CHRNA2 c.449+3A>T Uncertain significance ★★ same type
CHRNA2 c.73+4A>C Uncertain significance ★★ same type
CHRNA2 p.Ala177Pro Uncertain significance ★★ ⚠ same type
CHRNA2 p.Ala36Ser 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/chrna2-p-ser482pro (accessed [today's date]).

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