Is CHRNA7 p.Leu60Pro (c.179T>C) pathogenic?

CHRNA7 p.Leu60Pro (c.179T>C) is classified Uncertain significance in CHRNA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely pathogenic (0.9499); Absent from gnomAD v4.1.

How common is CHRNA7 p.Leu60Pro (c.179T>C) in the general population?

CHRNA7 p.Leu60Pro (c.179T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNA7 p.Leu60Pro (c.179T>C)?

AlphaMissense predicts likely pathogenic (score 0.9499) — an in-silico prediction, not a clinical call.

CHRNA7 p.Leu60Pro

c.179T>C · rs2504865666 · VCV2542657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9499 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9499	likely pathogenic
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.35	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 7.3	GERP 0.96, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 81 kb · p 0.98 · regional, not allelic
Overall
CADD	32.0	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: CHRNA7
Protein: p.Leu60Pro
Coding: c.179T>C
MANE Select: NM_000746
dbSNP: rs2504865666
Type: single nucleotide variant
Location: chr15:32031021 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 51 PDB
Residue 60: a β-strand

Full CHRNA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRNA7 p.Asn381Asp Uncertain significance ★★ ⚠ same type
CHRNA7 p.Val374Met Uncertain significance ★★ ⚠ same type
CHRNA7 c.196-4G>T Likely benign ★★ same type
CHRNA7 c.240+113C>A Benign ★★ same type
CHRNA7 c.350+304G>A Likely benign ★★ same type
CHRNA7 c.55+77G>A Benign ★★ same type
CHRNA7 c.598+86C>T Benign ★★ same type
CHRNA7 c.599-111T>A Benign ★★ 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/chrna7-p-leu60pro (accessed [today's date]).

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