Is SEPTIN7 p.Ser2Pro (c.4T>C) pathogenic?

SEPTIN7 p.Ser2Pro (c.4T>C) is classified Uncertain significance in SEPTIN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.2034); No allele count reported in gnomAD v4.1 (AN 1,517,140).

How common is SEPTIN7 p.Ser2Pro (c.4T>C) in the general population?

SEPTIN7 p.Ser2Pro (c.4T>C) is no allele count reported in gnomAD v4.1 (AN 1,517,140) (gnomAD).

What do computational predictors say about SEPTIN7 p.Ser2Pro (c.4T>C)?

AlphaMissense predicts likely benign (score 0.2034) — an in-silico prediction, not a clinical call.

SEPTIN7 p.Ser2Pro

c.4T>C · VCV4162616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2034 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,517,140)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2034	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 1.80	unconstrained · MANE · 32 kb · p 9.2e-06 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,517,140). 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: SEPTIN7
Protein: p.Ser2Pro
Coding: c.4T>C
MANE Select: NM_001788
Type: single nucleotide variant
Location: chr7:35801213 (GRCh38)
Gene constraint: LOEUF 0.313 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.75 · 8 PDB
Residue 2: a modified residue (n-acetylserine)

Full SEPTIN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SEPTIN7 p.Ser2Leu Uncertain significance ★ ⚠ same residue
SEPTIN7 c.872+1G>A Uncertain significance ★ same type
SEPTIN7 p.Arg243His Uncertain significance ★ ⚠ same type
SEPTIN7 p.Arg381Gln Uncertain significance ★ ⚠ same type
SEPTIN7 p.Arg402Cys Uncertain significance ★ ⚠ same type
SEPTIN7 p.Asn188Ser Uncertain significance ★ ⚠ same type
SEPTIN7 p.Asp140Val Uncertain significance ★ ⚠ same type
SEPTIN7 p.Gln206His Uncertain significance ★ ⚠ 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/septin7-p-ser2pro (accessed [today's date]).

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