Is CHRNA5 p.Pro162Ser (c.484C>T) pathogenic?

CHRNA5 p.Pro162Ser (c.484C>T) is classified Uncertain significance in CHRNA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: ambiguous (0.4916); Very rare (popmax 8.47e-05%, nfe).

How common is CHRNA5 p.Pro162Ser (c.484C>T) in the general population?

CHRNA5 p.Pro162Ser (c.484C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CHRNA5 p.Pro162Ser (c.484C>T)?

AlphaMissense predicts ambiguous (score 0.4916) — an in-silico prediction, not a clinical call.

CHRNA5 p.Pro162Ser

c.484C>T · VCV4228465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4916	ambiguous
REVEL	0.479	indeterminate
SaProt	LLR -9.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 28 kb · p 2.9e-05 · regional, not allelic
Overall
CADD	24.2	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 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 6.84e-05% 1/1,461,762 alleles · very rare

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: CHRNA5
Protein: p.Pro162Ser
Coding: c.484C>T
MANE Select: NM_000745
Type: single nucleotide variant
Location: chr15:78589875 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.04

Full CHRNA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNA5 p.Gln18= Benign ★★ same type
CHRNA5 p.Gly31= Benign ★★ same type
CHRNA5 p.Leu363Gln Benign ★★ ⚠ same type
CHRNA5 p.Lys167Arg Benign ★★ ⚠ same type
CHRNA5 p.Thr331= Benign ★★ same type
CHRNA5 p.Thr359Met Likely benign ★★ same type
CHRNA5 p.Tyr58= Benign ★★ same type
CHRNA5 c.304-96C>A 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/chrna5-p-pro162ser (accessed [today's date]).

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