Is MID2 p.Ala150Ser (c.448G>T) pathogenic?

MID2 p.Ala150Ser (c.448G>T) is classified Uncertain significance in MID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.693); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 101.

What condition is associated with MID2 p.Ala150Ser (c.448G>T)?

MID2 p.Ala150Ser (c.448G>T) is associated with intellectual disability, X-linked 101 (ClinVar).

How common is MID2 p.Ala150Ser (c.448G>T) in the general population?

MID2 p.Ala150Ser (c.448G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MID2 p.Ala150Ser (c.448G>T)?

AlphaMissense predicts likely pathogenic (score 0.693) — an in-silico prediction, not a clinical call.

MID2 p.Ala150Ser

c.448G>T · rs375785745 · VCV224103

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.693 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 101

Computational evidence

Protein change
AlphaMissense	0.693	likely pathogenic
REVEL	0.648	pathogenic-leaning
SaProt	LLR -10.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 101 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

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: MID2
Protein: p.Ala150Ser
Coding: c.448G>T
MANE Select: NM_012216
dbSNP: rs375785745
Type: single nucleotide variant
Location: chrX:107841113 (GRCh38)
Structure: AlphaFold pLDDT 80.18 · 4 PDB

Full MID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 101 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MID2 p.Ser60= Benign ★★ same condition
MID2 p.Arg164His Uncertain significance ★ same condition
MID2 p.Ile103Ser Uncertain significance ★ ⚠ same condition
MID2 p.Thr125Ala Uncertain significance ★ ⚠ same condition
MID2 p.Arg121His Uncertain significance ★★ ⚠ same type
MID2 p.Arg164Gly Uncertain significance ★★ ⚠ same type
MID2 p.Thr194= Benign/Likely benign ★★ same type
MID2 p.Arg105Pro 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/mid2-p-ala150ser (accessed [today's date]).

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