Is CHRNA7 p.Ser20Phe (c.59C>T) pathogenic?

CHRNA7 p.Ser20Phe (c.59C>T) is classified Uncertain significance in CHRNA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). AlphaMissense: ambiguous (0.4876); Absent from gnomAD v4.1.

How common is CHRNA7 p.Ser20Phe (c.59C>T) in the general population?

CHRNA7 p.Ser20Phe (c.59C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRNA7 p.Ser20Phe (c.59C>T)?

AlphaMissense predicts ambiguous (score 0.4876) — an in-silico prediction, not a clinical call.

CHRNA7 p.Ser20Phe

c.59C>T · rs754876538 · VCV1703980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4876 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4876	ambiguous
REVEL	0.499	indeterminate
SaProt	LLR -12.24	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 81 kb · p 0.98 · regional, not allelic
Overall
CADD	26.4	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: CHRNA7
Protein: p.Ser20Phe
Coding: c.59C>T
MANE Select: NM_000746
dbSNP: rs754876538
Type: single nucleotide variant
Location: chr15:32030901 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 51 PDB

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

Similar variants

CHRNA7 p.Ser20= Likely benign ★ same residue
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

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-ser20phe (accessed [today's date]).

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