Is SENP7 p.Leu826Val (c.2476C>G) pathogenic?

SENP7 p.Leu826Val (c.2476C>G) is classified Uncertain significance in SENP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1117); Very rare (popmax 0.00179%, amr).

How common is SENP7 p.Leu826Val (c.2476C>G) in the general population?

SENP7 p.Leu826Val (c.2476C>G) is very rare (popmax 0.00179%, amr) (gnomAD).

What do computational predictors say about SENP7 p.Leu826Val (c.2476C>G)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

SENP7 p.Leu826Val

c.2476C>G · VCV4582371

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -11.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 18 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	19.95	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

Grpmax group 0.00179% Admixed American · 1/55,940 alleles

Filtering AF 0.000456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000332%

Overall 0.000721% 11/1,526,150 alleles · very rare exomes 9/1,373,988 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00179%	55,940
European (non-Finnish)	0.000901%	110,976

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SENP7
Protein: p.Leu826Val
Coding: c.2476C>G
MANE Select: NM_020654
Type: single nucleotide variant
Location: chr3:101337513 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 57.05 · 2 PDB
Residue 826: the 'protease' region

Full SENP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SENP7 p.Asn308Ser Benign/Likely benign ★★ same type
SENP7 p.Asp637Tyr Benign ★★ same type
SENP7 p.Gln241His Benign ★★ same type
SENP7 p.Ser134= Benign ★★ same type
SENP7 p.Thr242Ser Benign ★★ same type
SENP7 p.Arg1030Trp Likely pathogenic ★ same type
SENP7 p.Gln325Ter Pathogenic ★ same type
SENP7 p.Gln492Ter Likely pathogenic ★ 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/senp7-p-leu826val (accessed [today's date]).

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