Is SENP7 p.Ser668Pro (c.2002T>C) pathogenic?

SENP7 p.Ser668Pro (c.2002T>C) is classified Uncertain significance in SENP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.016%, afr).

How common is SENP7 p.Ser668Pro (c.2002T>C) in the general population?

SENP7 p.Ser668Pro (c.2002T>C) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about SENP7 p.Ser668Pro (c.2002T>C)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

SENP7 p.Ser668Pro

c.2002T>C · VCV3439694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.085, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 18 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	17.49	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.016% African / African-American · 12/74,916 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000744% 12/1,613,836 alleles · ultra-rare exomes 4/1,461,634 · genomes 8/152,202 · joint denominator

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.Ser668Pro
Coding: c.2002T>C
MANE Select: NM_020654
Type: single nucleotide variant
Location: chr3:101343790 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 57.05 · 2 PDB

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-ser668pro (accessed [today's date]).

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