Is SCN7A p.Pro71Arg (c.212C>G) pathogenic?

SCN7A p.Pro71Arg (c.212C>G) is classified Uncertain significance in SCN7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.1589); No allele count reported in gnomAD v4.1 (AN 1,531,156).

How common is SCN7A p.Pro71Arg (c.212C>G) in the general population?

SCN7A p.Pro71Arg (c.212C>G) is no allele count reported in gnomAD v4.1 (AN 1,531,156) (gnomAD).

What do computational predictors say about SCN7A p.Pro71Arg (c.212C>G)?

AlphaMissense predicts likely benign (score 0.1589) — an in-silico prediction, not a clinical call.

SCN7A p.Pro71Arg

c.212C>G · VCV3793248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1589 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,531,156)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1589	likely benign
REVEL	0.825	moderately pathogenic-leaning
SaProt	LLR -9.12	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 72 kb · p 0.11 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,531,156). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SCN7A
Protein: p.Pro71Arg
Coding: c.212C>G
MANE Select: NM_002976
Type: single nucleotide variant
Location: chr2:166477485 (GRCh38)
Gene constraint: LOEUF 1.124 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.18 · 2 PDB

Full SCN7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCN7A p.Val187Ile Uncertain significance ★★ ⚠ same type
SCN7A c.3028-9A>T Benign ★★ same type
SCN7A p.Ala1282Val Benign ★★ same type
SCN7A p.Ala1313= Benign/Likely benign ★★ same type
SCN7A p.Ala456Gly Likely benign ★★ same type
SCN7A p.Ala818Ser Likely benign ★★ same type
SCN7A p.Arg1106Gln Likely benign ★★ same type
SCN7A p.Arg1516Lys Likely 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/scn7a-p-pro71arg (accessed [today's date]).

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