Is CHRNA9 p.Val467Glu (c.1400T>A) pathogenic?

CHRNA9 p.Val467Glu (c.1400T>A) is classified Uncertain significance in CHRNA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9174); Absent from gnomAD v4.1.

How common is CHRNA9 p.Val467Glu (c.1400T>A) in the general population?

CHRNA9 p.Val467Glu (c.1400T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNA9 p.Val467Glu (c.1400T>A)?

AlphaMissense predicts likely pathogenic (score 0.9174) — an in-silico prediction, not a clinical call.

CHRNA9 p.Val467Glu

c.1400T>A · VCV4228483

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9174 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9174	likely pathogenic
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.93, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.72 · regional, not allelic
Overall
CADD	28.0	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

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: CHRNA9
Protein: p.Val467Glu
Coding: c.1400T>A
MANE Select: NM_017581
Type: single nucleotide variant
Location: chr4:40354480 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.07 · 4 PDB

Full CHRNA9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNA9 p.Val467Ala Uncertain significance ★ ⚠ same residue
CHRNA9 p.Ala22Asp Uncertain significance ★ ⚠ same type
CHRNA9 p.Ala263Pro Uncertain significance ★ ⚠ same type
CHRNA9 p.Ala305Thr Uncertain significance ★ ⚠ same type
CHRNA9 p.Ala31Thr Uncertain significance ★ same type
CHRNA9 p.Arg138Gln Uncertain significance ★ ⚠ same type
CHRNA9 p.Arg138Pro Uncertain significance ★ ⚠ same type
CHRNA9 p.Arg138Trp 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/chrna9-p-val467glu (accessed [today's date]).

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