Is MID1 p.Pro385Ala (c.1153C>G) pathogenic?

MID1 p.Pro385Ala (c.1153C>G) is classified Conflicting classifications of pathogenicity in MID1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.9397); Very rare (popmax 0.00268%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MID1 p.Pro385Ala (c.1153C>G)?

MID1 p.Pro385Ala (c.1153C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MID1 p.Pro385Ala (c.1153C>G) in the general population?

MID1 p.Pro385Ala (c.1153C>G) is very rare (popmax 0.00268%, nfe) (gnomAD).

What do computational predictors say about MID1 p.Pro385Ala (c.1153C>G)?

AlphaMissense predicts likely pathogenic (score 0.9397) — an in-silico prediction, not a clinical call.

MID1 p.Pro385Ala

c.1153C>G · rs200213912 · VCV1734623

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9397 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9397	likely pathogenic
REVEL	0.544	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 118 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.00268% European (non-Finnish) · 24/894,727 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00152%

Overall 0.00207% 25/1,209,065 alleles · very rare exomes 23/1,097,407 · genomes 2/111,658 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00268%	37,280
Admixed American	0.00219%	45,677

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: MID1
Protein: p.Pro385Ala
Coding: c.1153C>G
MANE Select: NM_000381
dbSNP: rs200213912
Type: single nucleotide variant
Location: chrX:10469829 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB
Residue 385: the fibronectin type-iii domain

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.Ala211Pro Uncertain significance ★★ ⚠ same condition
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

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-pro385ala (accessed [today's date]).

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