Is MID1 p.Arg495Ter (c.1483C>T) pathogenic?

MID1 p.Arg495Ter (c.1483C>T) is classified Pathogenic in MID1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-11-29). Very rare (popmax 0.000224%, nfe); Associated with X-linked Opitz G/BBB syndrome.

What condition is associated with MID1 p.Arg495Ter (c.1483C>T)?

MID1 p.Arg495Ter (c.1483C>T) is associated with X-linked Opitz G/BBB syndrome (ClinVar).

How common is MID1 p.Arg495Ter (c.1483C>T) in the general population?

MID1 p.Arg495Ter (c.1483C>T) is very rare (popmax 0.000224%, nfe) (gnomAD).

MID1 p.Arg495Ter

c.1483C>T · rs745554420 · VCV523781

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

Conditions

X-linked Opitz G/BBB syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000224% European (non-Finnish) · 2/894,818 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,210,903 alleles · very rare exomes 2/1,097,393 · genomes 0/113,510 · 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.Arg495Ter
Coding: c.1483C>T
MANE Select: NM_000381
dbSNP: rs745554420
Type: single nucleotide variant
Location: chrX:10455042 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB
Residue 495: the b30.2/spry domain; the 'disordered' region

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

Disease context

X-linked Opitz G/BBB syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MID1 p.Arg495Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MID1 p.Ala130Thr Pathogenic/Likely pathogenic ★★ same condition
MID1 p.Arg277Ter Pathogenic ★★ same condition
MID1 p.Arg368Ter Pathogenic ★★ same condition
MID1 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
MID1 p.Arg36His Uncertain significance ★★ ⚠ same condition
MID1 p.His159Arg Uncertain significance ★★ ⚠ same condition
MID1 p.Ile555Val 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-arg495ter (accessed [today's date]).

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