Is SPIN4 p.Met148Ile (c.444G>A) pathogenic?

SPIN4 p.Met148Ile (c.444G>A) is classified Uncertain significance in SPIN4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely pathogenic (0.8579); Absent from gnomAD v4.1.

How common is SPIN4 p.Met148Ile (c.444G>A) in the general population?

SPIN4 p.Met148Ile (c.444G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPIN4 p.Met148Ile (c.444G>A)?

AlphaMissense predicts likely pathogenic (score 0.8579) — an in-silico prediction, not a clinical call.

SPIN4 p.Met148Ile

c.444G>A · VCV3961099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8579 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8579	likely pathogenic
REVEL	0.31	indeterminate
SaProt	LLR -8.15	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 746 bp · p 2.5e-07 · regional, not allelic
Overall
CADD	23.8	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: SPIN4
Protein: p.Met148Ile
Coding: c.444G>A
MANE Select: NM_001012968
Type: single nucleotide variant
Location: chrX:63350376 (GRCh38)
Structure: AlphaFold pLDDT 82.17 · 2 PDB
Residue 148: the 'tudor-like domain 2' region; a β-strand

Full SPIN4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPIN4 p.Arg144Leu Uncertain significance ★ ⚠ same type
SPIN4 p.Arg37Gly Uncertain significance ★ ⚠ same type
SPIN4 p.Arg38Lys Uncertain significance ★ ⚠ same type
SPIN4 p.His207Gln Uncertain significance ★ ⚠ same type
SPIN4 p.Ser117Cys Uncertain significance ★ ⚠ same type
SPIN4 p.Ser2Tyr Uncertain significance ★ ⚠ same type
SPIN4 p.Tyr163Ser Uncertain significance ★ ⚠ same type
SPIN4 p.Tyr184His 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/spin4-p-met148ile (accessed [today's date]).

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