Is MID1 p.Arg257Ser (c.769C>A) pathogenic?

MID1 p.Arg257Ser (c.769C>A) is classified Conflicting classifications of pathogenicity in MID1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-20). AlphaMissense: ambiguous (0.3988); No allele count reported in gnomAD v4.1 (AN 1,192,953); Associated with X-linked Opitz G/BBB syndrome.

What condition is associated with MID1 p.Arg257Ser (c.769C>A)?

MID1 p.Arg257Ser (c.769C>A) is associated with X-linked Opitz G/BBB syndrome (ClinVar).

How common is MID1 p.Arg257Ser (c.769C>A) in the general population?

MID1 p.Arg257Ser (c.769C>A) is no allele count reported in gnomAD v4.1 (AN 1,192,953) (gnomAD).

What do computational predictors say about MID1 p.Arg257Ser (c.769C>A)?

AlphaMissense predicts ambiguous (score 0.3988) — an in-silico prediction, not a clinical call.

MID1 p.Arg257Ser

c.769C>A · rs755644971 · VCV1708775

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3988 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,192,953)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

X-linked Opitz G/BBB syndrome

Computational evidence

Protein change
AlphaMissense	0.3988	ambiguous
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 118 kb · p 3.3e-08 · regional, not allelic
Overall
CADD	22.0	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

No allele count reported in gnomAD v4.1 (AN 1,192,953). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MID1
Protein: p.Arg257Ser
Coding: c.769C>A
MANE Select: NM_000381
dbSNP: rs755644971
Type: single nucleotide variant
Location: chrX:10495679 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB

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.Arg257Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MID1 p.Arg257His Uncertain significance ★ ⚠ same residue
MID1 p.Ala130Thr Pathogenic/Likely pathogenic ★★ same condition
MID1 p.Arg277Ter Pathogenic ★★ same condition
MID1 p.Arg368Ter Pathogenic ★★ same condition
MID1 p.Arg495Ter Pathogenic ★★ same condition
MID1 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
MID1 p.Arg36His 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-arg257ser (accessed [today's date]).

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