Is MID1 p.Val411Met (c.1231G>A) pathogenic?

MID1 p.Val411Met (c.1231G>A) is classified Uncertain significance in MID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.6393); Very rare (popmax 0.00112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MID1 p.Val411Met (c.1231G>A)?

MID1 p.Val411Met (c.1231G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MID1 p.Val411Met (c.1231G>A) in the general population?

MID1 p.Val411Met (c.1231G>A) is very rare (popmax 0.00112%, nfe) (gnomAD).

What do computational predictors say about MID1 p.Val411Met (c.1231G>A)?

AlphaMissense predicts likely pathogenic (score 0.6393) — an in-silico prediction, not a clinical call.

MID1 p.Val411Met

c.1231G>A · VCV4107893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6393 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6393	likely pathogenic
REVEL	0.24	benign-leaning
SaProt	LLR -13.30	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 118 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	24.9	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 0.00112% European (non-Finnish) · 10/894,453 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000826% 10/1,210,477 alleles · very rare exomes 10/1,096,922 · genomes 0/113,555 · joint denominator

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.Val411Met
Coding: c.1231G>A
MANE Select: NM_000381
Type: single nucleotide variant
Location: chrX:10469751 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB
Residue 411: 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-val411met (accessed [today's date]).

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