Is CHRNA6 p.Asp187Ala (c.560A>C) pathogenic?

CHRNA6 p.Asp187Ala (c.560A>C) is classified Uncertain significance in CHRNA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: ambiguous (0.5392); Absent from gnomAD v4.1.

How common is CHRNA6 p.Asp187Ala (c.560A>C) in the general population?

CHRNA6 p.Asp187Ala (c.560A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNA6 p.Asp187Ala (c.560A>C)?

AlphaMissense predicts ambiguous (score 0.5392) — an in-silico prediction, not a clinical call.

CHRNA6 p.Asp187Ala

c.560A>C · VCV3833201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5392 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5392	ambiguous
REVEL	0.9	moderately pathogenic-leaning
SaProt	LLR -9.67	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.41 · regional, not allelic
Overall
CADD	24.9	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: CHRNA6
Protein: p.Asp187Ala
Coding: c.560A>C
MANE Select: NM_004198
Type: single nucleotide variant
Location: chr8:42756639 (GRCh38)
Gene constraint: LOEUF 1.053 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.06 · 2 PDB
Residue 187: a β-strand

Full CHRNA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNA6 p.Ser266= Benign ★★ same type
CHRNA6 p.Arg109His Uncertain significance ★ ⚠ same type
CHRNA6 p.Arg330His Uncertain significance ★ ⚠ same type
CHRNA6 p.Arg376Gly Uncertain significance ★ ⚠ same type
CHRNA6 p.Arg96Cys Uncertain significance ★ ⚠ same type
CHRNA6 p.Asn402His Uncertain significance ★ ⚠ same type
CHRNA6 p.Asp119Asn Uncertain significance ★ ⚠ same type
CHRNA6 p.Asp129Asn 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/chrna6-p-asp187ala (accessed [today's date]).

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