Is MID1 p.Ala211Pro (c.631G>C) pathogenic?

MID1 p.Ala211Pro (c.631G>C) is classified Uncertain significance in MID1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-23). AlphaMissense: likely benign (0.3223); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MID1 p.Ala211Pro (c.631G>C)?

MID1 p.Ala211Pro (c.631G>C) is associated with Inborn genetic diseases (ClinVar).

How common is MID1 p.Ala211Pro (c.631G>C) in the general population?

MID1 p.Ala211Pro (c.631G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MID1 p.Ala211Pro (c.631G>C)?

AlphaMissense predicts likely benign (score 0.3223) — an in-silico prediction, not a clinical call.

MID1 p.Ala211Pro

c.631G>C · VCV3372210

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3223 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3223	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -2.83	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 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 118 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	22.3	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

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: MID1
Protein: p.Ala211Pro
Coding: c.631G>C
MANE Select: NM_000381
Type: single nucleotide variant
Location: chrX:10566917 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB

Full MID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MID1 p.Arg291Thr Uncertain significance ★★ ⚠ same condition
MID1 p.Arg472Cys Uncertain significance ★★ ⚠ same condition
MID1 p.Asn234Lys Uncertain significance ★★ ⚠ same condition
MID1 p.Asp180Asn Uncertain significance ★★ ⚠ same condition
MID1 p.Gly529Ala Uncertain significance ★★ ⚠ same condition
MID1 p.Ser225Asn Uncertain significance ★★ ⚠ same condition
MID1 p.Thr393Ile Uncertain significance ★★ ⚠ same condition
MID1 p.Ala196= Benign/Likely benign ★★ same condition

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/mid1-p-ala211pro (accessed [today's date]).

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